Virus-induced proteins functions

Among the retroviruses " are types B and C oncoviruses which induce malignant tumors in mammals and birds and the human immunodeficiency virus (HIV), the apparent causative agent of AIDS. Their RNA functions in a surprising way. Each virion contains a reverse transcriptase, an enzyme that transcribes copies of circular dsDNA copies from the one or two mRNA-like molecules that make up the virus genome. Following action of the reverse transcriptase, one of the transcribed DNA circles becomes covalently spliced into the host s own cellular DNA. There it remains permanently as a provirus. RNA molecules transcribed from the provirus serve as mRNA for virus-encoded proteins and also as the genomes for new virus particles. 

Various viruses encode proteins with sequenee homology to host proteins which are known to be involved in host defense functions. Viruses pirate and modify key immunoregulatory molecules, by use of molecular mimicry, to elude the Immune system (Murphy, 1997). Viruses also encode proteins that exploit or alter their host cells, replicate or induce migration for virus dissemination. Interestingly, DNA viruses such as the Herpesviruses (Cytomegalovirus (CMV), human herpesvirus (HHV-6 and 7), herpesvirus Saimiri (HVS) and Kaposi s sarcoma-associated Herpesvirus (KSHV)) all express GPCRs (Table 2). 

An alternative type of explanation for the specific discrimination against host cell protein synthesis in poliovirus-infected cells stemmed from the observation that initiation of protein synthesis could be selectively inhibited in HeLa cells and in poliovirus-infected HeLa cells by increasing the osmolarity of the growth medium (Sa-borio et al., 1974). The inhibition was independent of the solute used to increase the osmolarity. However, virus-directed protein synthesis was observed to be relatively more resistant to inhibition by hypertonic medium than was cellular protein synthesis, a fact which was interpreted as indicating that initiation of viral RNA translation was intrinsically more efficient than that of cellular mRNA (Nuss et al., 1975). These workers, therefore, proposed that the virus-specific or virus-induced factor involved in suppression of host protein synthesis could function by indiscriminantly lowering the rate of peptide chain initiation. Under such conditions, translation of viral mRNA, when it was synthesized, could occur due to its inherently strong affinity... 

Yamazaki and Wagner (1970) found that pretreatment of primary rabbit kidney cells with highly purified rabbit interferon greatly reduced VSV replication and inhibited synthesis of virus-specific proteins despite this inhibition of viral protein synthesis, interferon did not prevent the switch-off by VSV of cellular protein synthesis. This observation was interpreted, in retrospect erroneously, to be due to an input virion component rather than a newly synthesized viral product. It was originally thought that primary transcription of VSV is inhibited in interferon-treated cells (Marcus et al., 1971 Manders et al., 1972), but it now seems clear that only secondary transcription and not primary transcription is inhibited in interferon-pretreated cells (Repik et al., 1974). There is now quite convincing evidence that the interferon-induced inhibitor of VSV replication functions at the translational level (Sen, 1982). These circumstantial data point to the hypothesis that a VSV transcription product, alone or in association with another factor, is the inhibitor of cellular protein synthesis. 

If this partially purified fraction does not selectively inhibit protein synthesis as was shown to be the case with the purified cores (Person and Beaud, 1980), then its function in vaccinia virus-induced shut-off is not clear. Its mode of action is certainly different from that... 

In extension of the above investigation, Enouf et (31) studied the effect of S-adenosyl-L-homocysteine analogs on both protein methylase I and transformation of chicken embryo fibroblasts by Rouse sarcoma virus, and found that most of the analogs derived from alteration of the cysteine moiety were the most potent inhibitors for both functions. Furthermore, there was a direct correlation between the inhibition of protein methylase I activity and the inhibition of virus-induced cell transformation All the good inhibitors of protein methylase I activity strongly prevented the virus-induced cell transformation. 

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

Ebnet K, Kaldjian EP, Anderson AO, Shaw S (1996) Orchestrated information transfer underlying leukocyte endothelial interactions. Annu Rev Immunol 14 155-177 Edinger AL, Blanpain C, Kunstman KJ, Wohnsky SM, Parmentier M, Dorns RW (1999) Functional dissection of CCR5 coreceptor function through the use of CD4-independent simian immunodeficiency virus strains. J Virol 73(5) 4062 073 Edwards TG, Hoffman TL, Baribaud E, Wyss S, LaBranche CC, Romano J, Adkinson J, Sharron M, Hoxie JA, Dorns RW (2001) Relationships between CD4 independence, neutralization sensitivity, and exposure of a CD4-induced epitope in a human immunodeficiency virus type 1 envelope protein. J Virol 75(ll) 5230-5239... 

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