Virus life cycle

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

Nearly 40 million people are infected with the human immunodeficiency virus (HIV). Over half of those infected reside in sub-Saharan Africa. Worldwide during 2004, it is estimated that nearly 14,000 people a day were infected. Human immunodeficiency virus type 1 is the primary etiological source for the acquired immunodeficiency syndrome (AIDS). Fortunately, people infected with HIV are leading longer and more productive lives due to the availability of more effective therapies. Better medicines have evolved due to the efforts of scientists worldwide who find targets and compounds that inhibit the virus life-cycle. The current treatment for HIV infection is via a drug cocktail that usually includes a protease inhibitor (PI), a nucleoside reverse transcriptase inhibitor (NRTI), and a non-nucleoside reverse transcriptase inhibitor (NNRTI). 

Despite some uncertainties as to the overall role of PVR in vivo, several studies link the importance of this receptor to the virus life cycle. Kaplan et al. showed that exposure of poliovirus to soluble PVR converted the 160S particle to the 135S form and that this was associated with reduced infectivity (Kaplan et al., 1990). Other investigators showed that antibody-coated poliovirus was unable to enter nonpermissive GHO cells bearing Fc receptors, whereas, in contrast, foot-and-mouth disease virus (FMDV) was able to utilize this alternative entry pathway (Mason et al, 1994). Thus, PVR selectively mediates conformational changes in the poliovirus particle that are associated with cell entry and confers virus infection of cultured cells. Further studies will be necessary to explain why the broad distribution of this receptor does not allow virus replication in many cell types in vivo. 

Evidence that fusion inhibition is the mode of action for the RSV inhibitors described above has been based on the generation of resistant virus with changes mapped to the F protein, time-of-addition experiments that indicate interference early in the virus life cycle and demonstration of activity in an assay that specifically differentiates inhibition of virus fusion from binding to host cell receptors [ 129-131]. Figure 4 provides a visual representation of the resistance mutations that have arisen in the RSV F protein in response to selective pressure from BABIM (5), VP-14637 (10), BMS-433771 (13), TMC-353121 (33), BTA-9881, P13 (38) and C15 (39), mapped onto the structure of the F protein. The levels of resistance to the individual molecules are summarized in Table 3. Most notably, there is... 

Learning about animal virus life cycles is interesting because it not only teaches us something about important human pathogens, but also extends the basic principles of information transfer between DNA, RNA, and protein that we discussed in earlier chapters. Animal viruses have been discovered which seem to utilize... 

Baker T.S., Olson N.H., and Fuller S.D. (1999). Adding the third dimension to virus life cycles three-dimensional reconstmction of icosahedral viruses from ciyo-electron micrographs. Microbiology and Molecular Biology Reviews. 862—922. 

These processes have proven difficult to examine at the molecular level for most viruses and therefore it has been difficult to specifically target these stages of the virus life cycle. Uncoating is for the most part mediated by cellular enzymes but like penetration, is often influenced by one or more virus proteins [32,33],... 

The virus life cycle is as follows (a) attachment to host cell surface at receptor or other cell surface macromolecule (b) penetration via pinocytosis (c) uncoating of viral DNA or RNA (d) formation of viral proteins and enzymes ... 

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