RNA viruses replication

There are many schemes by which RNA viruses replicate their genetic material. In each case, however, RNA viruses must be able to convert RNA to DNA (like the retroviruses) or they must be able to replicate RNA using an RNA-dependent RNA polymerase. 

Wang, S., White, K. A. (2007). Riboswitching on RNA virus replication. Proc Natl Acad Sci USA 104, 10406-10411. 

Represses poliovirus I and L rna virus replication tumoral cell growth stopped CARRAHER... 

Extracts from 152 plant species, representing 46 different families, were screened for effects on tobacco mosaic virus (TMV) replication in cucumber cotyledons. Twenty species have shown enough activity to warrant further study. Several members of the Caprifoliaceae family increased virus replication. An extract of Lonicera involucrata enlarged the virus lesions in local lesion hosts and produced a thirty fold increase in virus titer, but had no effect on virus replication in systemic hosts. The active material appears to affect the virus defense mechanism of local lesion hosts. An extract of common geranium is an active virus inhibitor. It inactivates TMV and TMV-RNA (ribonucleic acid) in vitro by forming non-infectious complexes. In vivo, it also inhibited starch lesion formation in cucumber cotyledons incited by TMV infection. 

Viral Proteases. Figure 1 Role of virally encoded proteases in the replication cycle of a retrovirus (HIV, part a) and of a (+)-strand RNA virus (HCV, part b). The numbers correspond to the following steps in the infectious cycle ... 

In contrast to retroviruses, proteolysis is an early event in the replication cycle of (+)-strand RNA viruses and both protease and polymerase inhibitors can be expected to halt the propagation of infectious viral particles from already infected cells. 

Stuyver LJ, McBrayer TR, Tharnish PM, Clark J, Hollecker L, Lostia S, Nachman T, Grier J, Bennett MA, Xie MY, Schinazi RF, Morrey JD, Inlander JL, Furman PA, Otto MJ (2006a) Inhibition of hepatitis C replicon RNA synthesis by beta-D-2 -deoxy-2 -fluoro-2 -C-methylcytidine a specific inhibitor of hepatitis C virus replication, Antivir Chem Chemother 17 79-87... 

Despite the availability of an effective HBV vaccine, the virus is still a major health problem with approximately 350 million persons infected worldwide. Hepatitis an infection of the liver that is caused by a variety of RNA viruses (hepatitis A virus, hepatitis B virus, hepatitis C virus). RNAi has been used to inhibit HBV replication both in vitro and in vivo (Carmona et al. 2006 Ely et al. 2008 Hamasaki et al. 2003 Klein et al. 2003 Konishi et al. 2003 Weinberg et al. 2007 Ying et al. 2003). HBV is a member of the Hepadnaviridae and its genome is a 3.2-kb double-stranded circular DNA. Synthetic siRNAs and shRNA expression constructs showed potent inhibition of HBV replication in mice (Chen et al. 2005, 2007 GUadi et al. 2003 McCaffrey et al. 2003 Morrissey et al. 2005b Shin et al. 2006 Wu et al. 2005b ... 

Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C, Bowman K, Shaffer CS, Pohsky BA, Zinnen S (2005a) Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41 1349-1356... 

Wang Z, Ren L, Zhao X, Hung T, Meng A, Wang J, Chen YG (2004) Inhibition of severe acute respiratory syndrome virus replication by small interfering RNAs in mammalian ceUs, J Virol 78 7523-7527... 

Fig. 1 Antiviral genes inhibit virus replication at different stages of the viral life cycle. Early inhibitors prevent the establishment of the viral genome in the target cell (class I, e.g., entry inhibitors, RT inhibitors for HIV). Intermediate inhibitors prevent viral gene expression or amplification of the viral genome (class II, e.g., siRNAs, antisense RNAs). Late inhibitors prevent virion assembly or release, or inactivate the mature virions (class III, e.g., transdominant core proteins, capsid-targeted virion inactivation, CTVI). A list of antiviral genes in each class is found in Table 1...

Like HIV and other RNA viruses, HCV replicates as a quasispecies due to a high level of viral replication in combination with an error-prone replication strategy. Therefore, the issue of drug-resistance is expected to be a major challenge in this case as well. Indeed, resistance to HCV antiviral agents has already been... 

Enzymes in viruses We have stated that virus particles do not carry out metabolic processes. Outside of a host cell, a virus particle is metabolically inert. However, some viruses do contain enzymes which play roles in the infectious process. For instance, many viruses contain their own nucleic acid polymerases which transcribe the viral nucleic acid into messenger RNA once the infection process has begun. The retroviruses are RNA viruses which replicate inside the cell as DNA intermediates. These viruses possess an enzyme, an RNA-dependent DNA popo called reverse transcriptase, which transcribes the information in the incoming RNA into a DNA intermediate. It should be noted that reverse transcriptase is unique to the retroviruses and is not found in any other viruses or in cells. 

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