Information

What does common viruses found in the body weigh?

What does common viruses found in the body weigh?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

On NPR public radio news it was said that if the bacteria that is natural that assist in body function or just present in your body was put it into a ball it would weigh more or less 7 ounces (approximately 200 grams). I tried to find the exact quote but am still looking for it and will revise when I find it.

Can viruses assist in body function as in extending life in any way?

Can a body be 100% free of viruses of not how much would the total virus weigh if put in a ball?


Viruses, in general, are obligately pathogenic i.e. they don't usually co-exist (as commensals or symbionts) with our body cells. Their mechanism of survival involves usurping of the host cell machinery to produce their own proteins and genetic material. However, as pointed out in the comments, there are some viruses such as the GBV-C which can infect the host but seldom cause any disease. Moreover, this virus has been shown to have a positive effect on the innate immune response and inhibitory effect on HIV [1].

(Also, have a look at: Do beneficial viruses exist? If so, what examples are there?)

In our genome, here are some remnants of viruses that had infected our ancestors long back in past. A prominent example is that of retrotransposons. Retrotransposons are DNA sequences that constitute a significant part of our genome and they are structurally similar to the genome of retroviruses (like HIV). Retrotransposons had been considered junk DNA in the past but recent studies have shown that they do play some important roles in our body. For example, L1 retrotransposons cause somatic diversity (genetic diversity at the cellular level) of neurons and may possibly contribute to increasing the plasticity of our brain[2,3]. Retrotransposons can also regulate gene expression[4].

Other than that, there may be infectious viruses that are present in the body but are dormant. These may become active later (when the conditions are conducive) and cause the disease in that individual or spread to another person.

You can perhaps calculate the weight of these viral remnants (retrotransposons). It won't provide any great insight to anyone. You just have to calculate the percentage of genome these DNA sequences occupy and multiply it with molecular weight of the genomic DNA and total number of cells in the body. I'll leave that exercise to you.


Components of Viruses (4 Components)

It represents the viral chromosome. Nucleoid or viral chromosome is made of a single molecule of nucleic acid. It may be linear or circular with various degrees of coiling. Nucleoid is the infective part of virus.

The nucleic acid is either DNA or RNA but never both. DNA containing viruses are called de-oxy-viruses while RNA-containing viruses are termed as riboviruses. Each of them has two subtypes, double stranded and single stranded.

(i) Double Stranded or dsDNA:

It occurs in T2, T4 bacteriophages, coli-phage Lambda, Cauliflower Mosaic, Pox Virus, Adenovirus, Herpes Virus (linear), Polyoma Virus, Simian Virus-40 (SM40), Hepatitis В (circular).

(ii) Single Stranded or ssDNA:

Coli-phage MS 2, Coli-phage fd (linear), Coli-phage ф x 174 (circular). The single strand of DNA is called plus strand. A complementary or negative strand DNA is synthesized to produce DNA duplex for replication during multiplication of virus.

(iii) Double Stranded or dsRNA:

It is found in Reovirus and Tumour Virus (both linear)

(iv) Single Stranded or ssRNA:

The condition is more common in riboviruses The single strand RNA is generally linear, e.g., Poliomyelitis Virus, Foot and Mouth disease Virus, Influenza Virus, Tobacco Mosaic Virus (TMV), Tobacco Necrosis Virus Potato Mosaic Virus, Bean Mosaic Virus, Retroviruses.

Retroviruses have two copies of single stranded RNA (hence diploid), e.g., HIV (Human Immunodeficiency Virus, HTLV-III, AIDS Virus) HTLV-1 HTLV-11 (Human T-lymph trophic Viruses), Rous Sarcoma Virus (RS V of M).

In some riboviruses, the RNA can directly function as template and take: part in replication (e.g. TMV, Influenza Virus, Paramyxo Virus). In other riboviruses, the RNA of the nucleoid is first employed in synthesizing complementary DNA through reverse transcription (e.g., Oncogenic Viruses, HIV).

Because of the latter, these viruses are called retroviruses. The viral chromosome or nucleoid does not contain many genes. T4 bacteriophage contains about 100 genes. Viral chromosome or nucleic acid is coiled with the help of some polyamines or internal proteins.

Component # 2. Capsid (Sheath, Coat):

It is the proteinaceous covering around the virus which protects the nucleoid from damage from physical and chemical agents. The capsid consists of a number of subunits called capsomeres or capsomers. The capsid of TMV has 2130 capsomeres. In binal bacteriophages the capsid sheath of tail is contractile.

Component # 3. Envelope:

It is a loose membranous covering that occurs in some animal viruses, rarely plant and bacterial viruses. In contrast to enveloped viruses, the viruses without an envelope are called naked.

Envelope consists of proteins from (virus), lipids and carbohy­drates (from host). It has subunits called peplomeres or peplomers. Surface of envelope can be smooth or have outgrowths called spikes. Common enveloped viruses are HIV, Herpes Virus, Vaccinia Virus, etc.

Component # 4. Enzymes:

They are occasional. Enzyme lysozyme is present in the region that comes in contact with host cell in bacteriophages. Other enzymes are neuraminidase in Influenza Virus, RNA polymerase, RNA transcriptase, reverse transcriptase.


What does common viruses found in the body weigh? - Biology

Figure 1 – Geometry of bacteriophages. (A) Electron microscopy image of phi29 and T7 bacteriophages as revealed by electron microscopy. (B) Schematic of the structure of a bacteriophage. (A adapted from S. Grimes et al., Adv. Virus Res. 58:255, 2002.)

In terms of their absolute numbers, viruses appear to be the most abundant biological entities on planet Earth. The best current estimate is that there are a whopping 10 31 virus particles in the biosphere. We can begin to come to terms with these astronomical numbers by realizing that this implies that for every human on the planet there are nearly Avogadro’s number worth of viruses. This corresponds to roughly 10 8 viruses to match every cell in our bodies. The number of viruses can also be contrasted with an estimate of 4-6 x 10 30 for the number of prokaryotes on Earth (BNID 104960). However, because of their extremely small size, the mass tied up in these viruses is only approximately 5% of the prokaryotic biomass. The assertion about the total number of viruses is supported by measurements using both electron and fluorescence microscopy. For example, if a sample is taken from the soil or the ocean, electron microscopy observations reveal an order of magnitude more viruses than bacteria (≈10/1 ratio, BNID 104962). These electron microscopy measurements are independently confirmed by light microscopy measurements. By staining viruses with fluorescent molecules, they can be counted directly under a microscope and their corresponding concentrations determined (e.g. 10 7 viruses/ml).

Table 1: Sizes of representative key viruses. The viruses in the table are organized according to their size with the smallest viruses shown first and the largest viruses shown last. The organization by size gives a different perspective than typical biological classifications which use features such as the nature of the genome (RNA or DNA, single stranded (ss) or double stranded (ds)) and the nature of the host. Values are rounded to one or two significant digit.

Organisms from all domains of life are subject to viral infection, whether tobacco plants, flying tropical insects or archaea in the hot springs of Yellowstone National Park. However, it appears that it is those viruses that attack bacteria (i.e. so called bacteriophages – literally, bacteria eater – see Figure 1) that are the most abundant of all with these viruses present in huge numbers (BNID 104839, 104962, 104960) in a host of different environments ranging from soils to the open ocean.

Figure 2: Structures of viral capsids. The regularity of the structure of viruses has enabled detailed, atomic-level analysis of their construction patterns. This gallery shows a variety of the different geometries explored by the class of nearly spherical viruses. HIV and influenza figures are 3D renderings of virions from the tomogram..(Symmetric virus structures adapted from T. S. Baker et al., Microbiol. Mol. Biol. Rev. 63:862, 1999. HIV structure adapted from J. A. G. Briggs et al., Structure 14:15, 2006 and influenza virus structure adapted from A. Harris, Proceedings of the National Academy of Sciences, 103:19123, 2006.)

As a result of their enormous presence on the biological scene, viruses play a role not only in the health of their hosts, but in global geochemical cycles affecting the availability of nutrients across the planet. For example, it has been estimated that as much as 20% of the bacterial mass in the ocean is subject to viral infection every day (BNID 106625). This can strongly decrease the flow of biomass to higher trophic levels that feed on prokaryotes (BNID 104965).

Figure 3: The P30 protein dimer serves as a measure tape to help create the bacteriophage PRD1 capsid.

Viruses are much smaller than the cells they infect. Indeed, it was their remarkable smallness that led to their discovery in the first place. Researchers were puzzled by remnant infectious elements that could pass through filters small enough to remove pathogenic bacterial cells. This led to the hypothesis of a new form of biological entity. These entities were subsequently identified as viruses.

Viruses are among the most symmetric and beautiful of biological objects as shown in Figure 2. The figure shows that many viruses are characterized by an icosahedral shape with all of its characteristic symmetries (i.e. 2-fold symmetries along the edges, 3-fold symmetries on the faces and 5-fold rotational symmetries on the vertices, figure 2). The outer protein shell, known as the capsid, is often relatively simple since it consists of many repeats of the same protein unit. The genomic material is contained within the capsid. These genomes can be DNA or RNA, single stranded or double stranded (ssDNA, dsDNA, ssRNA or dsRNA) with characteristic sizes ranging from 10 3 -10 6 bases (BNID 103246, 104073. With some interesting exceptions, a useful rule of thumb is that the radii of viral capsids themselves are all within a factor of ten of each other, with the smaller viruses having a diameter of several tens of nanometers and the larger ones reaching diameters several hundreds of nanometers which is on par with the smallest bacteria (BNID 103114, 103115, 104073). Representative examples of the sizes of viruses are given in Table 1. The structures of many viruses such as HIV have an external envelope (resulting in the label “enveloped virus”) made up of a lipid bilayer. The interplay between the virus size and the genome length can be captured via the packing ratio which is the percent fraction of the capsid volume taken by viral DNA. For phage lambda it can be calculated to be about 40% whereas for HIV it is more than 10 times lower (BNID 111591).

Some of the most interesting viruses have structures with less symmetry than those described above. Indeed, two of the biggest viral newsmakers, HIV and influenza, sometimes have irregular shapes and even the structure from one influenza or HIV virus particle to the next can be different. Examples of these structures are shown in Figure 2. Why should so many viruses have a characteristic length scale of roughly 100 nanometers? If one considers the density of genetic material inside the capsid, a useful exercise for the motivated reader, it is found that the genomic material in bacterial viruses can take up nearly as much as 50% of the volume. Further, the viral DNA often adopts a structure which is close packed and nearly crystalline to enable such high densities. Thus, in these cases if one takes as a given the length of DNA which is tied in turn to the number of genes that viruses must harbor, the viruses show strong economy of size, minimizing the required volume to carry their genetic material.

To make a virus, the monomers making up the capsid can self assemble one mechanism is to start from some vertex and extend in a symmetric manner. But what governs the length of a facet, i.e. the distance between two adjacent vertices that dictates the overall size of a viron? In one case, a nearly linear 83 residue protein serves as a molecular tape measure helping the virus to build itself to the right size. The molecular players making this mechanism possible are shown in Figure 3. A dimer of two 15 nm long proteins defines distances in a bacteriophage which has a diameter of about 70 nm.

The recently discovered gigantic mimivirus and pandoravirus are about an order of magnitude larger (BNID 109554, 111143). The mechanism that serves to set the size of remains an open question. These viruses are larger than some bacteria and even rival some eukaryotes. They also contain genomes larger than 2 Mbp long (BNID 109556) and challenge our understanding of both viral evolution and diversity.


Interferons: Meaning, Production and Applications

Interferons are natural glycoproteins produced by virus-infected eukaryotic cells which protect host cells from virus infection. They were discovered by Isaacs and Lindenmann in 1957 in course of a study of the effect of UV-inactivated influenza virus on chick chorioallantoic membrane kept in an artificial medium.

They observed that the infected membrane produced a soluble substance in the medium which could inhibit the multiplication of active influenza virus inoculated in fresh chick chorioallantoic membranes. The substance was called interferon because it interfered with intra­cellular multiplication of viruses.

Later observations confirmed that such host-produced antiviral substances were common to many viruses. Viral interference is a phenomenon observed when multiplication of one virus is inhibited by another virus. For instance, when influenza-A virus is inoculated into the allantoic cavity of an embryonated egg followed after 24 hr by influenza-B virus, the multiplication of influenza-B virus is partly or completely inhibited. The reason why influenza-B virus cannot multiply is that the influenza-A virus infected cells produce interferon which partly or totally inhibits multiplication of B virus. The interferon also protects cells from influenza A virus.

Characteristics of Interferons:

An outstanding feature of interferons is that they are host-cell-specific and not virus-specific. This means that interferons produced by mouse or chicken will not protect human cells against the same virus which induced interferon in the experimental animals. On the other hand, an interferon produced by a virus X in an animal will protect the animal also from other viruses.

This is because interferons do not interact directly with the viruses. But they induce the virus infected cells to synthesize antiviral proteins which inhibit viral multiplication. These proteins have a wide inhibitory spectrum. As a result, not only the interferon-inducing virus, but others are also inhibited.

The reason why interferon produced by one species does not protect another species is that the same virus produces different interferons in different species. It has been observed that interferons produced by different host species following infection by the same virus differ in molecular weight as well as in other properties, like isoelectric point etc. Not only different species produce different interferons, different tissues of the same animal produce different interferons.

All types of interferons are proteins having a comparatively low molecular weight ranging between 15,000 to 40,000 Daltons. Hence, they are non-dialyzable and destroyed by proteolytic enzymes. Interferons are fairly stable at low pH (pH2) and can withstand moderate temperature being stable at 37°C for an hour or so. They are produced in minute amounts by the infected cells as a longer precursor having 23 amino acid residues more than the mature molecule.

Human interferons are of three main types. These are called alpha interferons (α-IFN), beta-interferons (β-IFN) and gamma-interferons (γ-IFN). Alpha-interferon contains many subtypes. The total subtypes exceed 20 in number.

It is produced by the B-lymphocytes, monocytes and macrophages. β-IFN is produced by the fibroblasts in the connective tissues. γ-IFN is synthesized by the T-lymphocytes after they are activated by antigens. α-IFN has been shown to be coded by as many as 20 distinct chromosomal genes, indicating thereby that the subtypes of this interferon represent a family of closely related proteins.

β-IFN appears to be a glycoprotein. It is coded by a single human gene. All the genes of α-IFN and β-IFN are located on the short arm of human chromosome 9. α-IFN proteins are all 166 amino acid long (except one). They are non-glycosylated and the proteins are monomeric. The single β-IFN protein is also 166 amino acid long and a glycoprotein. It is dimeric.

Production of Interferons:

Interferons are produced by living animal cells, both in vivo as well as cultured cells. Interferon production and its antiviral activity require expression of cellular genes, and these functions are blocked by inhibitors of transcription and translation. Thus, virus-infected host cells fail to produce interferon in presence of actinomycin D, an inhibitor of eukaryotic RNA polymerase. When the inhibitor is added after 2 hr of infection, interferon production is not inhibited, suggesting that transcription is completed by that time.

Interferon production starts after initiation of viral maturation and continues for 20 to 50 hr after that. Then the production stops, due to formation of a repressor which presumably is formed or activated only when the interferon concentration in the producing cell exceeds a certain threshold concentration. Most of the interferon is transported from the producing cell to other neighbouring cells.

The substance in a virus that is responsible for interferon synthesis by the host cell is known as interferon inducer. The nature of this substance was identified by Merigan (1970) as double-stranded RNA. The activity seems to reside in polyribonucleotide’s with a high helical content. The double- stranded RNA viruses — like reoviruses — can act as interferon inducer without replication. Single- stranded RNA viruses can act as inducers only after replication when they form double-stranded replicative intermediates. DNA-viruses can also induce interferons, presumably due to overlapping transcription of viral DNA as observed in case of vaccinia vinus (Fig. 6.39).

Fungal viruses which have mostly double-stranded RNA genomes are also efficient inducers of interferons. Some synthetic polymers containing riboinosinic acid, ribocytidylic acid (Poly I: C) as well as those containing riboadenylic acid and ribouridylic acid (Poly A: U) are also good inducers. All interferon inducers are characterized by high molecular weight, high density of anionic groups and resistance to enzymatic degradation. DNA and DNA-RNA hybrids have been found to be ineffective as interferon inducers.

The induction of interferon synthesis concerns α- and β-interferon’s which belong to a single class, called Type I. Gamma-interferon belongs to a separate class, called Type II. The human Υ-interferon is the single representative of its type. The gene coding the y-interferon protein is located on the long arm of chromosome 12. The gene has three introns, while the genes of α- and β- interferons are without any introns. Gamma-interferon (human) has 146 amino acids and is an N-glycosylated tetrameric protein. It is induced by antigenic stimulation of T-lymphocytes.

In presence of the inducer which is viral ds-RNA, the α- and β-interferon genes of the host chromosome(s) are activated to produce interferon m-RNAs. Those are then translated intoα- and β- interferon proteins. These proteins at first accumulate in the producing cell and eventually leave the cell to reach neighbouring host cells.

As the interferon concentration in the producing cell rises above a threshold level, it activates another gene of the producing cell which codes for a repressor protein which feeds back and stops further synthesis of interferon. As a result, virus-infected cells generally produce only small quantities of interferons.

The interferon molecules that leave the producing cell reach the neighbouring uninfected host cells and interact with the cell membrane or nuclear membrane receptors of these cells. Thereby these cells are induced to synthesise antiviral proteins. These antiviral proteins are the actual agents that provides protection to these host cells against viral infection.

Mechanism of Action of Interferons:

Type I interferons include α-IFN and β-IFN. These interferons do not interact with the viruses directly causing their inhibition, but they induce the formation of antiviral proteins which are activated to inhibit viral multiplications. These interferon-regulated proteins (IRPs) act presumably by blocking synthesis of the macromolecular components necessary for viral multiplication.

A general scheme for mechanism of action of type I interferons is shown in Fig. 6.40:

Several interferon regulated host proteins (IRPs) have been identified, though all of them have not been fully characterized. Among the better known of these proteins are a protein kinase and an enzyme catalyzing the formation of a short polymer of adenylic acid, the 2′, 5′-oligoadenylate synthetase (2′-5′ A synthetase).

The protein kinase is induced by Type I interferons. It has to be activated by ds-RNA. The activated kinase catalyses phosphorylation of initiation factor (el F-2) thereby causing inhibition of protein synthesis (Fig. 6.41).

The 2′-5′-oligoadenylate synthetase is an enzyme also induced by Type I interferons which requires activation by ds-RNA like the protein kinase. The activated synthetase acts as an activator of an endonuclease, RNase L. The activated RNAse degrades viral ss-RNA (Fig. 6.42).

Another group of proteins, called Mx-proteins induced by α- and β-IFN are known to possess intrinsic antiviral activity, although the exact molecular mechanism by which they inhibit viral multiplication is not known. Mx-proteins have been reported to play a major controlling role in infections caused by influenza viruses in experimental animals as well as in humans.

Type II interferon includes g-IFN which is also known as immune IFN. Although g-IFN also possesses anti-viral activity, its major role is in the immunity through activation of cytotoxic T-lymphocytes which can destroy virus infected cells. Besides T-lymphocytes, other naturally occurring killer cells like macrophages and monocytes are also activated by g-IFN. Thus, in contrast to that of Type I interferons, the antiviral effect of g-IFN is expressed through activating the killer cells of the body which destroy the virus-infected cells.

Type II interferon induces the major histocompatibility antigens of human cells. Expression of these antigens is essential for immuno-potent cells to present foreign antigens to the T-lymphocytes during generation of specific immune responses.

IFN induced expression of these major histocompatibility antigens represents an important contribution of the antiviral activity of g-IFN through enhancement of the activity of cytotoxic T-lymphocytes. The activation of cytotoxic T-lymphocytes by y-IFN also implies its possible role in elimination of cancer cells which are recognized by the immune system of the body as foreign objects.

Applications of Interferons:

Interferons could be ideal agents for combating viral diseases. They inhibit viral multiplication at such low concentration which is non-toxic to uninfected cells. One interferon can inhibit many viruses. But there are certain draw-backs which stand in their use.

Firstly, for application in humans, interferon must be of human origin, though interferons produced in monkey kidney cell cultures are also effective in humans. Interferons are produced in very small quantities and it is difficult to get them in sufficient quantity in pure form for clinical application. Another factor is that interferons are effective only for short periods and as such can be used against only acute infections, like influenza.

The difficulty of obtaining sufficient quantity of pure interferon for clinical use has been overcome by cloning the α-IFN and β-IFN human genes in bacteria and yeast. By growing these transgenic organisms in mass culture, it has been possible to obtain clinically usable interferons in sufficiently large quantities. Alpha-interferon has been marketed in 1984 under the trade name Intron A.

In the following years, this biotechnologically produced interferon has been approved for clinical use against diseases like genital herpes caused by herpes-virus, hepatitis B and C. Beta-interferon has also been biotechnologically produced and marketed under the trade name Betaseron. It has been used in a disease called multiple sclerosis. A recombinant g-interferon has been found effective against an inherited chronic disease, called granulomatous disease.

The neutrophils of the affected individual are unable to kill the infectious bacteria. Application of y-IFN to such persons restores the ability of the neutrophils to kill bacteria. As the disease is chronic and inherited, the affected persons must take g-IFN throughout their life to remain normal.

Interferons are not only antiviral, but they have also anticancer activity. Clinical trials have shown that interferons have effect against only some types of tumours. Alpha-interferon has been approved for treating hairy-cell leukemia, and Kaposi’s sarcoma, a cancer that occurs in AIDS patients.

Gamma-interferon has been mainly used as an immuno-stimulant in cancer patients. Resistance against tumours in the body is controlled by the immune response against tumour antigens. The cytotoxic T-lymphocytes recognize these antigens as foreign and destroy them. Gamma-interferon can stimulate the cytotoxic function of T-lymphocytes and other natural killer cells of the body, thereby helping to control the tumour cells.


Biology Chapter 43

I. Each lmohocyte has a unique membrane receptor that recognizes one antigen
II. when the lymphocyte binds an antigen, it is activate and begins dividing to form many identical copies of itself
III. cloned lymphocytes have slight differences and are selected by the spleen for removal if they do not bind an antigen
IV. cloned cells descend from an activated lymphocyte and persist even after the pathogen is eliminated.

A) it enables a rapid defense against and antigen that has been previously encountered

B) it enables an animal to counter most pathogens almost instantly the first time they are encountered

C) It results in effector cells with specificity for a large number of antigens

A) one has a major role in antibody production, while the other has a major role in cytotoxicity

B) one binds a receptor called BCR (B-cell receptor), while the recognizes a receptor called TCR (T-cell receptor)

C) B cella are activated by free-floating antigens in the blood or mph. T cells are activated by membrane-bound antigens

I. B-cell receptors bind to epitopes
II. T-cell receptors bind to epitopes
III. There can be 10 or more different epitopes on each antigen
IV. There is a one-to-one correspondence between antigen and epitope

A) B- cell receptors and T-cell receptors

B) B-cell receptors and antibodies

C) T-cell receptors and antibodies

A) B cell contact antigen --> helper T cell is activated --> clonal selection occurs

B) body cell becomes infected with a virus --> new viral proteins appear
--> class I MHC molecule-antigen complex displayed on cell surface

C) complement is secreted --> B cell contacts antigen --> helper T cell activated --> cytokines released

I. pathogen is destroyed
II. lymphocytes secrete antibodies
III. antigenic determinants from the pathogen bind to antigen receptors on lymphocytes
IV. lymphocytes specific to antigenic determinants from pathogen become numerous
V. only memory cells remain

A) respond to T- independent antigens

C) stimulate a cytotoxic T cell

A) proteins secreted by antigen-presenting cells

B) receptors present on the surface of natural killer cells

C) molecules present on the surface of T cells where they interact with major histocompatibility (MHC) molecules

A) CD4, CD8, and plasma cells

B) cytotoxic and helper cells

C) plasma, antigen-presenting, and memory cells

A) B cells produce IgE antibodies

B) B cells release cytokines

C) cytotoxic T cells present the class II MHC molecule-antigen complex on their surface

A) the antibody having at least two binding regions

B) disulfide bridges between the antigens

C) bonds between class I and class II MHC molecules

I) the binding of antibodies to the surface of microbes
II) antibody-mediated agglutination of microbes
III) the release of cytokines by activated B cells

B) ingestion of interferon

C) placental transfer of antibodies

A) the immune system responds nonspecifically to antigens

B) the cowpox virus made antibodies in response to the presence of smallpox

C) there are some epitopes (antigenic determinants) common to both pox viruses

A) vaccination with a weakened form of the toxin

B) injection of antibodies to the toxin

C) injection of interleukin-1

A) the surface antigens of the pathogen stay the same

B) all of the surface antigens on the pathogen be identified

C) the pathogen has only one epitope

A) the rearrangement of V region genes in that clone of responsive B cells

B) a switch in the kind of antigen-presenting cell that is involved in the immune response

C) a patient's reaction to the first kind of antibody made by the plasma cells

A) the MHC proteins are made from several different gene regions that are capable of

rearranging in a number of ways

B) MHC proteins from one individual can only be of class I or class II

C) each of the MHC genes has a large number of alleles, but each individual only inherits two

A) even though Jane's blood type is a match to Bob's, her major histocompatability (MHC) proteins may not be a match

B) a blood type match is less stringent than a match required for transplant because blood is more tolerant of change

C) for each gene, there is only one blood allele but many tissue alleles

A) MHC molecules of the donor may stimulate rejection of the graft tissue, but bacteria lack MHC molecules

B) the tissue graft, unlike the bacterium, is isolated from the circulation and will not enter into an immune response

C) a bacterium cannot escape the immune system by replicating inside normal body cells


Virus Replication Cycle

While the replication cycle of viruses can vary from virus to virus, there is a general pattern that can be described, consisting of five steps:

  1. Attachment &ndash the virion attaches to the correct host cell.
  2. Penetration or Viral Entry &ndash the virus or viral nucleic acid gains entrance into the cell.
  3. Synthesis &ndash the viral proteins and nucleic acid copies are manufactured by the cells&rsquo machinery.
  4. Assembly &ndash viruses are produced from the viral components.
  5. Release &ndash newly formed virions are released from the cell.

Attachment

Outside of their host cell, viruses are inert or metabolically inactive. Therefore, the encounter of a virion to an appropriate host cell is a random event. The attachment itself is highly specific, between molecules on the outside of the virus and receptors on the host cell surface. This accounts for the specificity of viruses to only infect particular cell types or particular hosts.

Penetration or Viral Entry

Many unenveloped (or naked) viruses inject their nucleic acid into the host cell, leaving an empty capsid on the outside. This process is termed penetration and is common with bacteriophage, the viruses that infect bacteria. With the eukaryotic viruses, it is more likely for the entire capsid to gain entrance into the cell, with the capsid being removed in the cytoplasm. An unenveloped eukaryotic virus often gains entry via endocytosis, where the host cell is compelled to engulf the capsid resulting in an endocytic vesicle. An enveloped eukaryotic virus gains entrance for its nucleocapsid when the viral envelope fuses with the host cell membrane, pushing the nucleocapsid past the cell membrane. If the entire nucleocapsid is brought into the cell then there is an uncoating process to strip away the capsid and release the viral genome.

Synthesis

The synthesis stage is largely dictated by the type of viral genome, since genomes that differ from the cell&rsquos dsDNA genome can involve intricate viral strategies for genome replication and protein synthesis. Viral specific enzymes, such as RNA-dependent RNA polymerases, might be necessary for the replication process to proceed. Protein production is tightly controlled, to insure that components are made at the right time in viral development.

Assembly

The complexity of viral assembly depends upon the virus being made. The simplest virus has a capsid composed of 3 different types of proteins, which self-assembles with little difficulty. The most complex virus is composed of over 60 different proteins, which must all come together in a specific order. These viruses often employ multiple assembly lines to create the different viral structures and then utilize scaffolding proteins to put all the viral components together in an organized fashion.

Release

The majority of viruses lyse their host cell at the end of replication, allowing all the newly formed virions to be released to the environment. Another possibility, common for enveloped viruses, is budding, where one virus is released from the cell at a time. The cell membrane is modified by the insertion of viral proteins, with the nucleocapsid pushing out through this modified portion of the membrane, allowing it to acquire an envelope.

Active Virus Life Cycle by John Kellogg Via OER at Oregon State University


Since the beginning of the current outbreak last May, Ebola has been a near daily news story. Most articles have focused on the public health aspect of the disease in terms of its spread throughout West Africa, attempts to contain it, and efforts to set up viable health care stations near affected areas. An earlier article on our website explained why this epidemic has become the worst Ebola outbreak in history [1], but most coverage hasn’t devoted much space to the actual mechanics of the Ebola virus – what it is, how it gets into your cells, how it causes the characteristic hemorrhaging and fever, and, most importantly, how researchers and doctors are developing treatments for it. The rest of this article will aim to explore these topics.

How does the Ebola virus infect people?

Ebola virus contains a type of genetic material called RNA, which is similar to DNA and contains the blueprint for assembling new virus particles. Unlike animals and plants, which also use DNA as a repository of information, viruses are not technically alive because they are incapable of replicating without help. In order to create new viruses, the virus must infiltrate a living cell, where it hijacks the host cell’s machinery to fulfill its own goals. In order to get into the cell, Ebola must travel through the cell membrane, which is a barrier that protects the cell from its environment. However, all cells need nutrients, which must have ways of entering the cell the viruses hitch a ride into the cell via one of these established nutrient-uptake entryways. Ebola virus takes advantage of a non-specific engulfing process called macropinocytosis, which allows the virus to be “eaten” by a wave-like motion of the cell membrane (Figure 1) [2].

Once inside the cell, the virus hijacks the cell’s own machinery to create more copies of itself. Often, this appropriation of the cell’s replication machinery comes at the expense of the cell being able to make all of its own needed machinery, leading to the death of the cell or at least an inability to function properly. After all of the pieces for a new virus have been assembled, the viral pieces “bud” from the cell, using the cell’s own membrane to make a capsule for its safe travel to new cells nearby (Figure 1b).

How Ebola virus infects human cells. (A) The Ebola virus is enclosed in a package that contains RNA, its genetic “blueprint” for reproduction. (B) Ebola has a protein called glycoprotein that sticks out of its membrane and binds to receptors (in red) on the cell surface. (C) The binding of these receptors triggers a cell “eating” process called macropinocytosis, resulting in the virus being engulfed by a wave-like motion of the cell membrane. (D) Once inside the cell, the virus’ RNA is uncoated, at which point it hijacks the human cell’s proteins to create more copies of itself. (E) Once new viral particles have been assembled, they move to the cell membrane and “bud off,” at which point they can travel to infect new cells (F).

How does this cell-by-cell infection translate to the full-body symptoms of Ebola?

Ebola virus is characterized by a variety of symptoms, beginning with fever, headache, and muscle pain, followed by vomiting, diarrhea, and internal bleeding [3]. Upon entering the body, the virus targets specific cell types, including liver cells, cells in the immune system, and endothelial cells, which line the inside of blood vessels. Once inside the cells, one of the proteins made by the virus is called Ebola virus glycoprotein [4]. The glycoprotein can disrupt cell adhesion, so that cells have trouble sticking to each other and to a scaffold called the extracellular matrix, which in healthy tissue helps to hold the cells together. The loss of cell adhesion is detrimental to any solid tissue, and by infecting blood vessel cells, the virus causes the vessels to become leaky, leading to hemorrhaging and internal bleeding.

By targeting liver cells, the body’s ability to clear toxins out of the bloodstream is compromised, and by infecting the immune system, whose cells travel everywhere in the body, Ebola has an opportunity to increase rapidly its area of infection. Over time, infection of cells throughout the body can cause organ failure, while fever, internal bleeding, diarrhea and vomiting can cause severe loss of electrolytes, blood plasma, and fluid. Ultimately, organ failure and shock caused by the internal bleeding lead to death [5].

What is the science behind treatments in development?

Researchers are exploring several avenues for treating Ebola. Many drug companies are developing vaccines, although none of these vaccines is ready for full-scale production, or even approved for human treatment [6]. These vaccines use non-virulent portions of the virus injected into the body, to teach the immune system to recognize the Ebola virus and defend your body against it in the event of a true infection. Although the vaccines would usually be months or even years away from approval, emergency protocols approved by the World Health Organization have determined that this epidemic warrants the use of unapproved drugs and vaccines, so cautious plans are being made to expand access to Ebola victims [7,8].

A second treatment being developed uses small fragments of genetic material called “small interfering RNAs” (siRNAs). These small pieces of RNA are designed to match specific pieces of the virus’ RNA. Just like two pieces of Velcro sticking together, when the siRNA encounters the corresponding viral piece of RNA, it sticks to it. Once stuck to the siRNA, the viral RNA cannot be used to create new Ebola particles, thus slowing the replication of the virus. The FDA has recently approved siRNA therapy for use in the current outbreak [9].

Another treatment which has been used for several health-care workers who became infected with Ebola virus involves the use of antibodies. Antibodies are large, Y-shaped proteins that are designed to recognize and neutralize foreign objects in your body, such as bacteria or viruses. Currently, the most well developed drug is called ZMapp, which is a cocktail of three antibodies. The antibodies have a “lock” on the tip of the Y that recognizes a specific “key” – in this case, a specific portion of the Ebola virus glycoprotein described in the previous section. Once bound, the antibodies neutralize the glycoprotein, which subsequently keeps the virus out of the cell. So far, data about its efficacy in humans has been inconclusive, as the patients did not all receive the drug at the same point in the course of their disease, nor did they receive the same levels of medical care [10]. ZMapp or other similar drugs are important as tools to treat already infected patients during an outbreak, but unlike a vaccine, they do not confer lifelong immunity to the virus. This ultimately means that exploring both vaccines and drug treatments may be the most effective way to combat Ebola.

Even if experimental drugs can be scaled up to have large enough quantities to treat the current epidemic, the traditional methods of treatment will continue to be paramount for saving lives. In order to stave off shock from loss of blood and fluids, patients in health-care facilities can be given infusions of blood, fluids and electrolytes to help their bodies remain stable while fighting the virus. In the immediate future, the major challenges in bringing this epidemic under control will continue to be a focus on its containment, coupled with an influx of health-care facilities and experts capable of delivering the best care possible in onerous conditions.

Ilana Kelsey is a student in the Biological and Biomedical Sciences graduate program.


References

[2] Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. (2018). “Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines”. Journal of Extracellular Vesicles. 7 (1): 1535750. doi:10.1080/20013078.2018.1535750. PMC 6322352. PMID 30637094.

[3] Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, et al. (2015). “Biological properties of extracellular vesicles and their physiological functions”. Journal of Extracellular Vesicles. 4: 27066. doi:10.3402/jev.v4.27066. PMC 4433489. PMID 25979354.

[4] van Niel G, D’Angelo G, Raposo G (April 2018). “Shedding light on the cell biology of extracellular vesicles”. Nature Reviews. Molecular Cell Biology. 19 (4): 213–228. doi:10.1038/nrm.2017.125. PMID 29339798.

[5] van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R (July 2012). “Classification, functions, and clinical relevance of extracellular vesicles”. Pharmacological Reviews. 64 (3): 676–705. doi:10.1124/pr.112.005983. PMID 22722893.

[6] Keller S, Sanderson MP, Stoeck A, Altevogt P (November 2006). “Exosomes: from biogenesis and secretion to biological function”. Immunology Letters. 107 (2): 102–8. doi:10.1016/j.imlet.2006.09.005. PMID 17067686.

[7] Spaull R, McPherson B, Gialeli A, Clayton A, Uney J, Heep A, Cordero-Llana Ó (April 2019). “Exosomes populate the cerebrospinal fluid of preterm infants with post-haemorrhagic hydrocephalus”. International Journal of Developmental Neuroscience. 73: 59–65. doi:10.1016/j.ijdevneu.2019.01.004. PMID 30639393.

[8] Dhondt B, Van Deun J, Vermaerke S, de Marco A, Lumen N, De Wever O, Hendrix A (June 2018). “Urinary extracellular vesicle biomarkers in urological cancers: From discovery towards clinical implementation”. The International Journal of Biochemistry & Cell Biology. 99: 236–256. doi:10.1016/j.biocel.2018.04.009. PMID 29654900.

[9] Wang J, Chen S, Bihl J, “Exosome-Mediated Transfer of ACE2 (Angiotensin-Converting Enzyme 2) from Endothelial Progenitor Cells Promotes Survival and Function.” Oxid Med Cell Longev, 2020 Jan 182020:4213541. doi: 10.1155/2020/4213541

[10] Mignot G, Roux S, Thery C, Ségura E, Zitvogel L (2006). “Prospects for exosomes in immunotherapy of cancer”. Journal of Cellular and Molecular Medicine. 10 (2): 376–88. doi:10.1111/j.1582-4934.2006.tb00406.x. PMC 3933128. PMID 16796806.

[11] Rubik, B. Bioelectromagnetic Medicine. Administrative Radiology Journal XVI(8), August 1997, 38-46.

[12] Young, R.O., “The Effects of ElectroMagnetic Frequencies (EMF) on the Blood and Biological Terrain.” https://www.drrobertyoung.com/…/the-effects-electromagnet-f…

[13] Young, R.O., “Adverse Health Effects of 5G Mobile Networking Technology Under Real-Life Conditions.” April 19th, 2020. https://www.drrobertyoung.com/…/adverse-health-effects-of-5…

[14] NOAA. (2016). In a high carbon dioxide world, dangerous waters ahead. (accessed on August 6, 2019)

[15] NOAA. (2018). What is Ocean Acidification? (accessed on August 6, 2019)

[16] National Geographic. (2017). Ocean Acidification. (accessed on August 6, 2019)

[17] NOAA. (2010). Ocean Acidification, Today and in the Future. (accessed on August 6, 2019)

[18] Young, R.O., Young, S.R, “The pH Miracle Revised and Updated.” Hachett Publishing, 2010.

[19] Are the Interstitial Fluids Raining Acid on YOUR Lung Cells? (December 17th, 2019)


Introduction to the Viruses

In 1898, Friedrich Loeffler and Paul Frosch found evidence that the cause of foot-and-mouth disease in livestock was an infectious particle smaller than any bacteria. This was the first clue to the nature of viruses, genetic entities that lie somewhere in the grey area between living and non-living states.

Viruses depend on the host cells that they infect to reproduce. When found outside of host cells, viruses exist as a protein coat or capsid, sometimes enclosed within a membrane. The capsid encloses either DNA or RNA which codes for the virus elements. While in this form outside the cell, the virus is metabollically inert examples of such forms are pictured below.

When it comes into contact with a host cell, a virus can insert its genetic material into its host, literally taking over the host's functions. An infected cell produces more viral protein and genetic material instead of its usual products. Some viruses may remain dormant inside host cells for long periods, causing no obvious change in their host cells (a stage known as the lysogenic phase). But when a dormant virus is stimulated, it enters the lytic phase: new viruses are formed, self-assemble, and burst out of the host cell, killing the cell and going on to infect other cells. The diagram below at right shows a virus that attacks bacteria, known as the lambda bacteriophage, which measures roughly 200 nanometers.

Viruses cause a number of diseases in eukaryotes. In humans, smallpox, the common cold, chickenpox, influenza, shingles, herpes, polio, rabies, Ebola, hanta fever, and AIDS are examples of viral diseases. Even some types of cancer -- though definitely not all -- have been linked to viruses.

Viruses themselves have no fossil record, but it is quite possible that they have left traces in the history of life. It has been hypothesized that viruses may be responsible for some of the extinctions seen in the fossil record (Emiliani, 1993). It was once thought by some that outbreaks of viral disease might have been responsible for mass extinctions, such as the extinction of the dinosaurs and other life forms. This theory is hard to test but seems unlikely, since a given virus can typically cause disease only in one species or in a group of related species. Even a hypothetical virus that could infect and kill all dinosaurs, 65 million years ago, could not have infected the ammonites or foraminifera that also went extinct at the same time.

On the other hand, because viruses can transfer genetic material between different species of host, they are extensively used in genetic engineering. Viruses also carry out natural "genetic engineering": a virus may incorporate some genetic material from its host as it is replicating, and transfer this genetic information to a new host, even to a host unrelated to the previous host. This is known as transduction, and in some cases it may serve as a means of evolutionary change -- although it is not clear how important an evolutionary mechanism transduction actually is.

The image of influenza virus was provided by the Department of Veterinary Sciences of the Queen's University of Belfast. The tobacco mosaic virus picture was provided by the Rothamstead Experimental Station. Both servers have extensive archives of virus images.

The Institute for Molecular Virology of the University of Wisconsin has a lot of excellent information on viruses, including news, course notes, and some magnificent computer images and animations of viruses.

The Cells Alive! website includes information on the sizes of viral particles and an article on the mechanisms of HIV infection.


New discoveries

Understanding the relationships between viruses began with noting similarities in size and shape, whether viruses contained DNA or RNA, and in which form. With better methods to sequence and compare viral genomes, and with the constant influx of new scientific data, what we know about viruses and their histories is constantly being fine-tuned.

Until 1992, the notion that viruses were much smaller than bacteria, with tiny genomes was taken for granted. That year scientists discovered a bacteria-like structure within some amoebae in a water-cooling tower, according to Wessner. As it turns out, what they discovered was not a bacterial species, but a very large virus, which they dubbed Mimivirus. The virus is about 750 nm in size and may also have the same staining properties as gram-positive bacteria. This was followed by the discovery of other large viruses such as the Mamavirus and Megavirus.

&ldquoIt is not known how these large viruses evolved,&rdquo Dudley said, referring to them as the &ldquoelephants&rdquo of the virus world. &ldquoThey may be degenerate cells, which have become parasites of other cells (Mimiviruses infect amoeba), or they may be more typical viruses that keep acquiring additional host genes,&rdquo she added. Mimiviruses require a host&rsquos cellular machinery to produce proteins, just like other smaller viruses. However, their genome still contains many remnants of genes associated with the process of translation. It is possible that Mimiviruses may have once been independent cells. Or they could have simply acquired and accumulated some host genes, Wessner wrote.

Such discoveries bring up new questions and open new avenues of research. In the future these studies may provide answers to fundamental questions about the origins of viruses, how they reached their present parasitic state, and whether viruses should be included in the tree of life.