Flavivirus replication

The 2 -C-methyl-substituted ribonucleosides 2 -C-methyladenosine and -guanosine were also found to inhibit the replication of flaviviruses other than HCV, such as bovine viral diarrhea virus (BVDV), yellow fever virus, and West Nile virus (Mighaccio et al. 2003). Other 2 -C-methylribonucleosides such as P-D-2 -deoxy-2 -lluoro-2 -C-methylcytidine (PSl-6130), however, showed little if any activity against BVDV, West Nile virus, or yellow fever virus (Stuyver et al. 2006). 

Despite the protective effect of NO against various viral infections, workers in several studies have shown a harmful role of NO in many systems. NO seems to play a part in the development of pneumonia caused by influenza virus [128], in the pathogenesis in mice of tick-borne encephalitis flavivirus infection [131], and in worsening the course of the murine myocarditis caused by coxsackievirus B3 [132]. In addition, pneumonia in mice induced by herpes simplex virus type 1 could be suppressed by the inhibitor of iNOS [133]. The issue of whether NO acts as an inhibitor of viral replication or as a harmful agent, therefore, remains unanswered. This issue is particularly evident in HIV-1 infection, since NO seems to act as a double-edged sword in the pathogenesis of HIV-1. 

Chambers TJ, Hahn CS, GaUer R, Rice CM (1990) Flavivirus genome organization, expression, and replication. Annu Rev Microbiol 44 649-88... 

The replication of alphaviruses and flaviviruses is supported by both vertebrate and invertebrate cells in tissue culture. Infection by either virus group in permissive vertebrate cells produces infectious viruses and inhibits host cell macromolecular synthesis leading to eventual host cell death, whereas, in permissive arthropod cells, in-... 

Flaviviruses are small, enveloped viruses, with cubic symmetry, approximately 45 nm in diameter, which replicate in vertebrate and invertebrate cells. The nucleocapsid contains the single-stranded plus RNA associated with a nucleocapsid protein, C, which has a molecular weight of 13K. The viral envelope consists of one large glycoprotein, E, of molecular weight approximately 55K, and a small 8K membrane-associated protein, M, which is not glycosylated (Wes-taway, 1980 Matthews, 1982). The structural components of flaviviruses have been reviewed by Russell et al. (1980) and the replication strategy of these viruses reviewed by Westaway (1980). 

Infection of A. albopictus cells with alphaviruses leads to the synthesis of maximum titers of infectious virus by approximately 24 hr postinfection (acute phase). At the acute phase, up to 85% of the cells released infectious virus (Davey and Dalgarno, 1974), and the rate of synthesis of intracellular 42 S and 26 S viral RNA and structural proteins is maximal. By 48 hr postinfection, viral 26 S RNA and protein syntheses are inhibited, and the proportion of cells releasing virus is dramatically reduced (Davey and Dalgarno, 1974 Eaton, 1979). Inhibition of 42 S RNA synthesis occurs at 3 days after infection (start of chronic phase see Fig. 2). The nature of the factor(s) responsible for inhibiting viral replication in infected mosquito cells at the chronic phase is not known. The fact that large amounts of 42 S RNA are made in infected mosquito cells 48 hr after infection, at a time when viral structural protein synthesis is inhibited, suggests that the replication inhibition factor may act initially at the level of viral protein synthesis (Eaton, 1979). Eaton demonstrated that viral structural protein synthesis is inhibited before a decrease in 26 S RNA synthesis is detected in SIN-infected A. albopictus cells. Thus, the biphasic nature of alphavirus infection is also observed in the case of flavivirus infection in mosquito cells (Paul et al., 1969). 

Thus, the togaviruses are able to replicate in arthropod cells and in a wide range of vertebrate cells. This wide host range implies that any functions supplied by the host during replication must be common to a broad phylogenetic range of organisms. This is a unique characteristic of alpha- and flaviviruses. 

Boulton, R. W., and Westaway, E. G., 1976, Replication of the flavivirus Kunjin Proteins, glycoproteins, and maturation associated with cell membrane, Virology 69 416. 

Wengler, G., and Wengler, G., 1981, Terminal sequences of the genome and rep-licative-form RNA of the flavivirus West Nile virus Absence of poly (A) and possible role in RNA replication. Virology 113 544. 

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