Vesicular stomatitis virus mechanism

Anti-hepatitis B virus activity in vitro and in vivo was also found in wogonin and baicalein (Fig. 4), the major active constituents of the traditional Chinese medicine Scutellaria radix.More recently, Blach-Olszewska et al investigated the effect of baicalein and wogonin on two important mechanisms of innate immunity The secretion of cytokines, and the natural resistance of human leukocytes to viral infection. The results obtained indicate that these fiavonoids modulate cytokine production, that is they inhibit interferons-a and -y, and stimulate tumor necrosis factor-a and interleukin production. They also augment the resistance of peripheral blood leukocytes to the vesicular stomatitis virus. 

In discussing the mechanism of antiviral protection and stimulation of interferon production in the mouse, DeClercq and Merigan46 concluded that there was a direct relationship between the extent of protection against vesicular stomatitis virus, the titers of interferon produced and the doses of tilorone. Giron et al.47, however, found no correlation between interferon induction and protection against MM virus in mice. Protection was achieved at doses far below the doses at which detectable interferon was found in the serum. Both findings may be consistent with differing mechanisms of viral inactivation for the two viruses under study. 

In both procedures, a gene encoding an abundant membrane glycoprotein (G protein) from vesicular stomatitis virus (VSV) Is Introduced Into cultured mammalian cells either by transfection or simply by Infecting the cells with the virus. The treated cells, even those that are not specialized for secretion, rapidly synthesize the VSV G protein on the ER like normal cellular secretory proteins. Use of a mutant encoding a temperature-sensitive VSV G protein allows researchers to turn subsequent protein transport on and off. At the restrictive temperature of 40 °C, newly made VSV G protein Is misfolded and therefore retained within the ER by quality control mechanisms discussed in Chapter 16, whereas at the permissive temperature of 32 C, the accumulated... 

Type I (IFN-a/P) and type II (IFN-y) IFNs are major lines of defense against viral infection. IFNs mediate direct antiviral effector mechanisms that inhibit multiple steps of viral replication (Samuel 1991 Vilcek and Sen 1996). For example, 2, 5 -oligoadenylate synthetase (2, 5 -OAS) activates ribonuclease L, which degrades mRNA and limits the accumulation of viral transcripts. Protein kinase R blocks translation of viral transcripts by phosphorylating translation initiation factor eIF-2. Mx proteins block influenza, vesicular stomatitis virus, and herpes simplex virus replication by an unknown mechanism. 

Baxt, B., and Bablanian, R., 1976a, Mechanism of vesicular stomatitis virus-induced cytopathic effects. I. Early morphological changes induced by infectious and DI particles, Virology 12 310. 

This short summary of the chemistry and biology of rhabdoviruses is intended to provide certain background information required to interpret the mechanisms by which rhabdoviruses perturb cell functions. These comments are not intended to serve as a comprehensive analysis of the structure and function of rhabdoviruses other reviews and current literature must be consulted for in-depth principles of rhabdovirology. Unless indicated otherwise, all properties described here refer to those of the Indiana serotype of vesicular stomatitis virus (VSV-Indiana), which serves as the prototypic model of all rhabdoviruses. 

A block at the level of initiation of protein synthesis has also been suggested as the mechanism of shut-off by vesicular stomatitis virus (VSV Stanners et al., 1977 Jaye et al., 1982 Gillies and Stollar, 1982). As in poliovirus-induced shut-off, degradation of host mRNAs does not seem to play a role in VSV-induced shut-off since host mRNA can be extracted from infected cells and translated in vitro (Ehrenfeld and Lund, 1977). However, recent work has demonstrated that the synthesis of VSV leader RNA is directly related to inhibition of host RNA synthesis (Grinnell and Wagner, 1983). Unlike poliovirus mRNAs, VSV mRNAs are capped and require cap-binding protein for translation (Banerjee, 1980 Rose et al., 1978). The mechanism of VSV-induced shut-off is presently under active investigation to determine if competition between mRNAs (Lodish and Porter, 1980,... 

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