Translation viral

Fig. 4. Diagrams of the El and E2 expression plasmids used to transcribe and translate viral gene products and diagram of the plasmid containing the BPV-1 replication origin.

In the second step, the virus synthesizes an inhibitor that inactivates an initiation factor and by the mid-point of infection, most ribosomes are directed towards translating viral mENA. This two step process could explain the differential effect of such perturbations as exposure to high salt concentrations and histidinol treatment on cellular and viral mENA translation and the inactivation of initiation factor eIF-4B after infection of HeLa cells with poliovirus. 

The shell of all picomaviruses is built up from 60 copies each of four polypeptide chains, called VPl to VP4. These are translated from the viral RNA into a single polypeptide, which is posttranslationally processed by stepwise proteolysis involving viraily encoded enzymes. First, the polypeptide chain is cleaved into three proteins VPO (which is the precursor for VP2 and VP4), VPl and VP3. These proteins begin the assembly process. The last step of the processing cascade occurs during completion of the virion assembly the precursor protein VPO is cleaved into VP2 and VP4 by a mechanism that is probably autocatalytic but may also involve the viral RNA. VPl, VP2, and VP3 have molecular masses of around 30,000 daltons, whereas VP4 is small, being 7000 daltons, and is completely buried inside the virion. 

HCV polymerase that carried the S282T mutation did no longer incorporate 2 -C-methyl-CTP during the initiation step of RNA synthesis (Dutartre et al. 2006). The presence of the S282T mutation induces a general reduction (5-20-fold) in terms of polymerase efficiency (Dutartre et al. 2006), which may translate to decreased viral fitness (Ludmerer et al. 2005). 

Interim results from the SPRINT-1 phase 2 trial of boceprevir (SCH 503034) have been released. In subjects who received boceprevir plus interferon-a and ribavirin, viral RNA loads were suppressed at week 12 in between 70 and 79% of subjects infected with genotype 1 HCV, compared with only 34% in the interferon-o/ ribavirin standard of care arm (www.sch-plough.com/schering plough/news/release. jsp releaseID = 1064540). However, it is not yet known if this enhanced early response will translate into sustained response. 

In terms of their molecular structures, the nucleotide and protein realms are usually considered to be rather independent of each other. However, these two families of molecules are covalently linked in the translational aminoacyl- RNAs and ribonucleoproteins as well as in the nucleoproteins involved in cellular and viral replication. In these hybrid biomolecules, a (deoxy)ribose phosphate moiety serves as the structural connection between the nucleoside and peptide moieties. 

Figure 38-10. Picornavimses disrupt the 4F complex. The 4E-4G complex (4F) directs the 40S ribosomal subunit to the typical capped mRNA (see text). 4G alone is sufficient for targeting the 40S subunit to the internal ribosomal entry site (IRES) of viral mRNAs. To gain selective advantage, certain viruses (eg, poliovirus) have a protease that cleaves the 4E binding site from the amino terminal end of 4G. This truncated 4G can direct the 40S ribosomal subunit to mRNAs that have an IRES but not to those that have a cap. The widths of the arrows indicate the rate of translation initiation from the AUG codon in each example.

The viral protein Rev may also play a role in HIV-1 latency. Expression of the viral Rev protein is essential for the nuclear export of genomic RNA as well as unspliced and/or singly spliced transcripts (Cullen 2003), which are ultimately translated into structural, regulatory, and enzymatic viral proteins. Retention of Rev and Tat (viral transactivator proteins) transcripts in the nucleus of resting CD4h- T cells from HAART patients (Lassen et al. 2006) might be involved in the maintenance of post-integration latency in these cells. Importantly, this phenomenon is non-existent in activated T cells. 

With some RNA vimses, e.g. poliovims, the RNA strand fi cm the particle can act directly as mRNA and is translated into viral proteins on the host-cell ribosomes. In many other RNA vimses, however (e.g. the influenza vimses), the RNA strands are negative-sense RNAs (anhmessages) that have first to be transcribed to the complementary sequence by RNA-dependent RNA polymerases before they can function in protein synthesis. Sinee eukaryotie eells do not have these enzymes, the negative-sense RNA vimses must earry them in the virion. 

A virus-specific RNA RNA polymerase is needed, since the cell RNA polymerase will generally not copy double-stranded RNA (and ribosomes are not able to translate double-stranded RNA either). A wide variety of modes of viral mRNA synthesis are outlined in Figure. By convention, the chemical sense of the mRNA is considered to be of the plus (+) configuration. The sense of the viral genome nucleic acid is then indicated by a plus if it is the same as the mRNA and a minus if it is of oppposite sense. If the virus has double-stranded DNA (ds DNA), then mRNA synthesis can proceed directly as in uninfected cells. However, if the virus has a singlestranded DNA (ss DNA), then it is first converted to ds DNA and the latter serves as the template for mRNA synthesis with the cell RNA polymerase. 

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