Viruses infection process

Fig. 17.13. Progressive changes in infrared absorbance of lower epidermis of cucumber cotyledons induced by the cucumber mosaic virus infection process (averaged values of two experiments).

When a virus multiplies, the genome becomes released from the coat. This process occurs during the infection process. The present chapter is divided into three parts. The first part deals with basic concepts of virus structure and function. The second part deals with the nature and manner of multiplication of the bacterial viruses (bacteriophages). In this part we introduce the basic molecular biology of virus multiplication. The third part deals with important groups of animal viruses, with emphasis on molecular aspects of animal virus multiplication. 

Enzymes in viruses We have stated that virus particles do not carry out metabolic processes. Outside of a host cell, a virus particle is metabolically inert. However, some viruses do contain enzymes which play roles in the infectious process. For instance, many viruses contain their own nucleic acid polymerases which transcribe the viral nucleic acid into messenger RNA once the infection process has begun. The retroviruses are RNA viruses which replicate inside the cell as DNA intermediates. These viruses possess an enzyme, an RNA-dependent DNA popo called reverse transcriptase, which transcribes the information in the incoming RNA into a DNA intermediate. It should be noted that reverse transcriptase is unique to the retroviruses and is not found in any other viruses or in cells. 

As we have noted, the outcome of a virus infection is the synthesis of viral nucleic acid and viral protein coats. In effect, the virus takes over the biosynthetic machinery of the host and uses it for its own synthesis. A few enzymes needed for virus replication may be present in the virus particle and may be introduced into the cell during the infection process, but the host supplies everything else energy-generating system, ribosomes, amino-acid activating enzymes, transfer RNA (with a few exceptions), and all soluble factors. The virus genome codes for all new proteins. Such proteins would include the coat protein subunits (of which there are generally more than one kind) plus any new virus-specific enzymes. 

Attachment There is a high specificity in the interaction between virus and host. The most common basis for host specificity involves the attachment process. The virus particle itself has one or more proteins on the outside which interact with specific cell surface components called receptors. The receptors on the cell surface are normal surface components of the host, such as proteins, polysaccharides, or lipoprotein-polysaccharide complexes, to which the virus particle attaches. In the absence of the receptor site, the virus cannot adsorb, and hence cannot infect. If the receptor site is altered, the host may become resistant to virus infection. However, mutants of the virus can also arise which are able to adsorb to resistant hosts. 

Consequences of virus infection in animal cells Viruses can have varied effects on cells. Lytic infection results in the destruction of the host cell. However, there are several other possible effects following viral infection of animal cells. In the case of enveloped viruses, release of the viral particles, which occurs by a kind of budding process, may be slow and the host cell may not be lysed. The cell may remain alive and continue to produce vims over a long period of time. Such infections are referred to as persistent infections. 

Kuzushita N, Hayashi N, Kanto T, Ta-kehara T, Tatsumi T, Katayama K et al. Involvement of transporter associated with antigen processing 2 (TAP2] gene polymorphisms in hepatitis C virus infection. Gastroenterology 1999 116[5] 1149-1154. 

Such sugar-dendrimer complexes ( sugar balls ) have been used to inhibit the interactions of viruses with cell surfaces. Many viruses bind to particular carbohydrate residues on cell surfaces, which in turn facilitate their entry into cells and the resultant infection process. A virus particle presents a multi-dentate surface consisting of many carbohydrate-binding proteins able to interact with multiple cell-surface carbohydrates. The surface of a dendrimer that is modified with... 

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The Producing System. The questions of particular concern here are the nature of the system used to manufacture the desired substance, and the precision with which it is controlled. If the system consists of prokaryotic cells, then how well-defined is their provenance and how is their consistency demonstrated If mammalian cells are employed, their lineage must be considered. In both instances, it is important to ensure that extraneous virus, infections, DNA and less well-defined factors such as slow viruses are excluded by the origins and history of the producer strain, or because the physical (e.g., filtration) or chemical (pH, solvents, affinity separation) nature of the production process can be relied upon to exclude passage of an infectious agent. 

Another potential class of antivirals is those that interfere with the ability of virus to enter cells. If the virus entry process is inhibited, then spread of infection within an individual might be inhibited. As discussed earlier, HIV virus particles initially attach to cells by way of the cellular receptor for CD4 protein, which is embedded in the surface of normal T lymphocytes and macrophages. Recently, recombinant DNA techniques have been used to make large amounts of a part of the pure CD4 protein. Test-tube experiments have shown that if this CD4 protein fragment is incubated with T lymphocytes or macrophages, it can saturate all the CD4 receptors and prevent subsequent infection with HIV. It is possible that this approach might be effective in people, as well. 

The tobacco mosaic virus (center right), a plant pathogen, has a structure similar to that of MB, but contains ssRNA instead of DNA. The poliovirus, which causes poliomyelitis, is also an RNA virus. In the influenza virus, the pathogen that causes viral flu, the nucleocapsid is additionally surrounded by a coat derived from the plasma membrane of the host cell (C). The coat carries viral proteins that are involved in the infection process. 

Pharmacology Tipranavir is a nonpeptidic HIV-1 PI that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1-infected cells, thus preventing formation of mature virions. 

Humoral Immune Response in Chronic Inflammatory Processes. The specificity of the diagnostically relevant intrathecal antibodies depends on the underlying cause of the disorder. In the case of chronic infective processes, the antibodies are exclusively targeted against the causative organism (F5). Increased IgC levels are found in about 30% of patients with chronic meningitis or encephalitis from various causes, such as bacteria, virus and protozoa, and in diseases like polyradiculitis, sarcoidosis, and chronic myelopathy (LI). 

In the Licari and Bailey Model [102] and also in the latest Hu and Bentley Model [105] it is proposed that the infection process be described by the Poisson distribution with mean and variance equal to a.MOI. The a-value has been proposed to be dependent on the physical system and a value of a = 0.04 was proposed for static systems [102]. For agitated systems suspension cultures Hu and Bentley proposed a value of a = 0.08 because they state that agitation systems enable higher efficiency of contact between viruses and cells [105]. This is not absolutely true, at least the true reason is not the higher mixing level but the fact that in static cultures, less cell surface is exposed to the virus, since to the cells are attached to a surface. This gives an overall constant of attachment 3-4 fold lower than in suspension systems [61]. 

We need to have drugs, antidotes, and cures for the weapons of mass destruction that terrorists are likely to use. To develop medicinal countermeasures, the basic science involved must first be understood. For both chemical and biological weapons, the process of molecular recognition by elements of the human body is of utmost importance. However, we do not have a clear understanding of protein surface interactions, the relationship of genes to protein function, and how viruses infect and replicate. All of these processes are chemical in nature and caimot be solved without knowledge of the chemical sciences. 

Canine parvovirus, first identified in 1978, is now endemic.455,456 Childhood fifth disease is also caused by a parvovirus.456,457 When these single-stranded DNA viruses infect cells a double-stranded replicative form of DNA arises by synthesis of the complementary negative strand alongside the original positive DNA strand. Many copies of the replicative form are then synthesized. The negative strands of the replicative forms serve as templates for synthesis of numerous new positive strands that are incorporated into the progeny viruses. The whole process may take only 20 minutes. Some parvoviruses are unable to reproduce unless the cell is also infected by a larger adenovirus. 

Bacteriophage, a virus infecting bacterial cells, has a structure somewhat different from those previously described. A head contains the nucleic acid and the viral DNA passes through a tail during the infection process. In the T-even phages (Fig. 1), the tad consists of a tube surrounded by a sheath and is connected to a thin collar al the head end and a plate at the tip end. The sheath is capable of contraction and the plate possesses pins and tail fibers, which are the organs of attachment of the bacteriophage to the. wall of the host cell. 

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