Viruses, RNA

Type I and II (HTLV I and II) are two closely related types with a high genomic similarity, tropic for CD4+ T-lymphocytes. HTLV I is associated with the adult T-cell lymphoma and leukemia in addition to some types of myelopathy. HTLV II might be involved in certain demyelinating diseases. HTLV-III has similarity to the Simian T-lymphotropic virus 3 (STLV-III) 

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The N-terminal part of the tomato bushy stunt virus polypeptide chain (the R-segment in Figure 16.8) is disordered in all the subunits. As in the core of many other single-strand RNA viruses this region of the polypeptide chain... 

Alphaviruses, such as Sindbis virus and Semliki Forest virus, are a group of mosquito-borne, enveloped RNA viruses that can cause encephalitis, fever, arthritis and rashes in mammals. These viruses have two protein shells—an outer glycoprotein layer and an inner core— which are separated by a lipid bilayer, a membrane. Studies by cryoelectron microscopy have shown that... 

Table 1. Picornavirus Characteristics (Very Small RNA Viruses)...

For example, treatment of dione 12 with hydrochloric acid yielded furan 13, a key synthetic intermediate for the production of a variety of compounds that were recently investigated for anticancer activity. Related inquiries by members of the same research team identified furans derived from IS as potential treatments for RNA viruses. Furan IS was prepared by condensation of dione 14 with catalytic sulfuric acid in refluxing acetic anhydride. ... 

Viral vectors are usually classified by the characteristics of the parental viius. Based on the viral genome, one can distinguish between DNA and RNA viruses (for details see [1, 2]). 

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 ... 

The infectious cycle of a (+)-strand RNA virus such as the hepatitis C virus differs by the fate of the viral RNA genome in the infected cell. Upon entry into the cell, the HCV genome is used as a messenger RNA to drive the synthesis of a large polyprotein precursor of about 3,000 residues [2]. The structural proteins are excised from the precursor by host cell signal peptidase. 

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. 

Petersen J, Dandri M, Mier W, Lfltgehetmann M, Volz T, von Weizsacker F, Haberkom U, Fischer L, Pollok JM, Erbes B, Seitz S, Urban S (2008) Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein, Nat Biotechnol 26 335-341 PorniUos O, Garrus JE, Sundquist WI (2002) Mechanisms of enveloped RNA virus budding. Trends CeU Biol 12 569-579... 

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

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 ... 

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... 

Many animal viruses, particularly the oncogenic viruses—either directly or, in the case of RNA viruses such as HIV that causes AIDS, their DNA transcripts generated by the action of the viral RNA-dependent... 

Methisazone (Fig. 5.2IB) inhibits DNA viruses (particularly vaccinia and variola) but not RNA viruses, and has been used in the prophylaxis of smallpox. It is now little used, especially as, according to the World Health Organization, smallpox has now been eradicated. 

Studies have demonstrated that one such method is to examine the effects of disinfectants on endogenous RNA-dependent DNA polymerase (i.e. reverse transcriptase) activity. In essence, HIV is an RNA virus after it enters a cell the RNA is converted to DNA under the influence of reverse transcriptase. The virus induces a cytopathic effect on T lymphocytes, and in the assay reverse transcriptase activity is determined after exposure to different concentrations of various disinfectants. However, it has been suggested that monitoring residual viral reverse transcriptase activity is not a satisfactory alternative to tests whereby infectious HIV can be detected in systems employing fresh human peripheral blood mononuclear cells. 

HCV is a small enveloped single-stranded RNA virus belonging to the Flaviviridae family and Hepacivirus genus [12]. Other Flaviviridae members include the flaviviruses such as yellow fever virus, and pestiviruses, which are responsible, for example, for bovine viral diarrhea [13]. The most closely related virus identified to date is GBV-B, which infects the tamarind, a new world monkey. GBV-B has also been tentatively classified as a Hepacivirus... 

Hepatitis A is a non-enveloped single-stranded ribonucleic acid (RNA) virus classified as the Hepatovirus genus under I the Picornaviridae family.1 The only host for the HAV is... 

Hepatitis C, first known as non-A, non-B hepatitis, is a blood-borne infection that is a single-stranded RNA virus belonging to the Flaviviridae family and the Hepacivirus genus.12 The... 

Hepatitis E is a non-enveloped single-stranded messenger RNA virus of unclassified genus.18 The HEV is similar to HAV in that the virus is harvested in contaminated feces, thus infecting people via the fecal-oral route. High HEV levels in the bile often prompt viral shedding in the feces. The severity of hepatic damage is dependent on the HEV strain Mex 14, Sar 55, or the US 2 strain.19 No cases of chronic hepatitis E have yet been documented. 

HCV is a single-stranded RNA virus of the Flaviviridae family. It has a 9.4-kb positive-sense genome encoding a polyprotein precursor of 3011 amino acids. Individual isolates of HCV consist of closely related yet heterogeneous populations... 

Figure 3.2 Relative sizes of some common viruses infecting humans. DNA viruses are green, RNA viruses are red.

We have also noted in Section 5.8 that the RNA of the cell is generally in the single-stranded configuration. Interestingly, although single-stranded RNA viruses are more common, viruses are known in which the RNA is in the double-stranded form. 

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