Vesicular stomatitis virus replication

The oncolytic viruses include adenovirus, measles, reovirus, vesicular stomatitis virus (VSV),HSV,poxvirus, and vaccinia. Specific examples include (1) ONYX-015, which is an adenoviral oncolytic virus, administered to patients with liver metastases of colorectal cancer and pancreatic cancer [29], (2) Reolysin, which is an oncolytic reovirus administered to patients with glioma [30], and (3) MV-CEA, which is an oncolytic measles virus expressing carcinoembryonic antigen, administered to patients with ovarian cancer [31]. Some oncolytic viruses are wild type and are apparently not pathogenic in humans, such as the Newcastle disease virus (NDV), which is an RNA avian paramyxovirus. PV701, a naturally attenuated, replication-competent strain of NDV, has been administered to patients with advanced solid tumors [32], The applicability of oncolytic viruses as a therapy for clinical oncology trials is due to their potential selectivity the ability to kill tumor cells but not normal cells. However, the level of attenuation of viral replication in normal cells is limited for most oncolytic vectors. 

PPIases also play a key role in cell entry and in the replication of several pathogenic viruses, as well as in the formation of mature virions. The vesicular stomatitis virus New Jersey serotype, which causes major diseases in animals, particularly cattle, contains several host proteins, including cyclophilin A, which are essential for viral replication. CsA and overexpression of catalytically inactive mutants of CypA drastically inhibit gene expression of the virus New Jersey serotype but have little effect on the virus Indiana serotype [102]. Although it is presently the subject of controversial publications and is still misunderstood, the involvement of PPIases - notably hCypl8 - in the HIV-1 life cycle is one of the most famous examples of the hijacking of host proteins by a lentivirus [8]. 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasally with vesicular stomatitis virus ( 5)-DHPA significandy increased survival from the infection. (3)-DHPA did not significandy reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of X-adenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of 5-adenosyhnethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block virus replication by interference with viral mRNA methylation. 

The nucleotide form of ribavirin does not manifest its antiviral activity simply by lowering the GTP levels, but may indeed participate directly in binding to specific G proteins (124). Ribavirin has recently been studied as an inhibitor of vesicular stomatitis virus and La Crosse virus (125). Of the phosphorylated forms of the drug, ribavirin-5 -diphosphate was by far the most potent inhibitor of viral replication for these two viruses. 

These cell-agglutinating proteins have been reported active against certain membrane-containing viruses. Concanavalin A (con A, from Canavalia ensiformis) was found to inactivate HSV, vesicular stomatitis virus (VSV), influenza virus and CMV infectivity and also found to interfere with the viral replication [11]. Other examples for these toxins are lentil lectin... 

The following aspects of viral glycoproteins have been reviewed glycoprotein and protein precursors to plasma membranes in vesicular stomatitis virus infected HeLa cells,membrane glycoproteins of enveloped viruses, membrane assembly, including the synthesis and intracellular processing of vesicular stomatitis virus, and the structure and replication of a-viruses. ... 

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. 

MBBK (Madin-Darby Bovine Kidney) cells are an established line of male bovine cells. Although restrictive for mengovirus replication, they have been used as a productive host for the WSN strain of influenza virus (21) and for vesicular stomatitis virus... 

It has been realized for some time that viral multiplication can occur with only minimal cytopathic effects (Choppin, 1964). Conversely, considerable cytopathology can result from infection with a virus, the multiplication of which is restricted in that host. Cantell et al. (1962) were perhaps the first to describe that L cells could be destroyed by large doses of a UV-irradiated virus, vesicular stomatitis virus, in the absence of a detectable synthesis of viral antigen this toxic activity could not be separated from the viral particle. We shall discuss in a later chapter why this does not prove the absence of viral replicative functions or that preformed virion components are necessarily cytotoxic. However, it is quite clear that early interactions... 

All functions of a cell need not remain intact to retain susceptibility to viral infections. However, loss of certain functions will predispose to resistance to certain viruses and not others. For example, cells enucleated by cytochalasin B will support the replication of vesicular stomatitis virus but not influenza virus, which also fails to inhibit protein synthesis in enucleated cells (Follett et al., 1974). 

Doyle and Holland, 1973) in the case of these DI particles of vesicular stomatitis virus, the only replicative event detectable is transcription of a 46-nucleotide leader sequence from the 3 end of the remaining segment of the viral genome (Emerson et al., 1977). 

Follett, E. A. C., Pringle, C. R., Wunner, W. H. and Skehel, J. J., 1974, Virus replication in enucleate cells Vesicular stomatitis virus and influenza virus, J. Virol. 13 394. 

Dubovi, E. J., and Youngner, J. S., 1976a, Inhibition of pseudorabies virus replication by vesicular stomatitis virus. I. Activity of infectious and inactivated B particles, J. Virol. 18 526. 

Hill, V. M., Marnell, L., and Summers, D. F., 1981,vitro replication and assembly of vesicular stomatitis virus nucleocapsids. Virology 113 109. 

Robertson, B. H., and Wagner, R. R., 1981, Host cell variation in response to vesicular stomatitis virus inhibition of RNA synthesis, in The Replication of Negative Strand Viruses (D. H. L. Bishop and R. W. Compans, eds.), pp. 955-963, Elsevier North Holland, Amsterdam. 

Wertz, G. W., 1978, Isolation of possible replicative intermediate structures from vesicular stomatitis virus infected cells. Virology 85 271. 

Wertz, G. W., 1983, Replication of vesicular stomatitis virus defective interfering particle RNA in vitro Transition from synthesis of defective interfering leader RNA to synthesis of full-length defective-interfering RNA, J. Virol. 46 513. 

Wilusz, J., Kurilla, M. G., and Keene, J. D., 1984, La protein binds to a unique species of minus sense leader RNA during the replication of vesicular stomatitis virus, Proc. Natl. Acad. Sci. USA 80 5827. 

Besides the role of retinoids in host immune defenses to viral infections (see [6] for review), retinoids may also affect virus replication. Angulo et al. [44] characterized three RA response elements in the promoter region of human cytomegalovirus (hCMV) and demonstrated the necessity for RAR and RXR in the viral promoter s positive response to RA. In contrast, the replication of herpes simplex virus-1 (HSV-1) in cultured Vero cells was inhibited by isomers of RA, but not retinol inhibition occurred without evident induction of IFN-a or IFN-p gene expression [45]. RA also protected HL-60 and WISH cells from infection with vesicular stomatitis virus (VSV) [46] however, in this case RA significantly increased the ability of IFN-a to decrease virus replication. These apparently contrasting effects of RA on hCMV as compared to HSV-1 or VSV replication further illustrate the potential for retinoids to act either positively or negatively in host resistance to viral infection and anti-viral immunity. Retinoid-IFN interactions are further discussed later in this chapter. 

---