Viruses RNA viruses

The third major difficulty in developing cold cures arises from the fact that the HRVs are RNA viruses. When presented with any selective pressure, including chemotherapeutic or antibody challenge, RNA viruses mutate rapidly [9]. This ability to mutate is most clearly illustrated in influenza viruses (RNA viruses), where new strains continuously arise to circumvent immunity in a population. Influenza A viruses have been shown to mutate around the anti-influenza drug Amantadine, after a single passage through a susceptible human host. The mutated viruses shed from a host treated with Amantadine are now resistant to Amantadine. These mutated viruses appear to be as virulent as the parent strain of virus [10]. 

Nakamura S, Katamine S, Yamamoto T, Foung SK, Kurata T, Hirabayashi Y, Shimada K, Hino S, Miyamoto T. Amplification and detection of a single molecule of human immunodeficiency virus RNA. Virus Genes 1993 7(4) 325-338. 

Buchschacher GL Jr, Wong-Staal F. Etiology of cancer viruses RNA viruses. In DeVita VT Jr, Heilman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 7th Ed. Baltimore Lippincott Williams Wilkins, 2005 165-173. 

The viruses responsible for AIDS are human immunodeficiency virus 1 and 2 (HIV 1 and HIV 2) Both are retroviruses, meaning that their genetic material is RNA rather than DNA HI Vs require a host cell to reproduce and the hosts m humans are the T4 lymphocytes which are the cells primarily responsible for inducing the immune system to respond when provoked The HIV penetrates the cell wall of a T4 lymphocyte and deposits both its RNA and an enzyme called reverse transcriptase inside There the reverse transcriptase catalyzes the formation of a DNA strand that is complementary to the viral RNA The transcribed DNA then serves as the template from which the host lymphocyte produces copies of the virus which then leave the host to infect other T4 cells In the course of HIV reproduction the ability of the T4 lymphocyte to reproduce Itself IS compromised As the number of T4 cells decrease so does the body s ability to combat infections... 

A virus is a species containing DNA and RNA that can reproduce itself, but to do this, it needs to hijack the metabolism (cells) of a host organism, since it has no information itself with which to build cells. 

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Reverse transcriptase (from avian or murine RNA tumour viruses) [9068-38-6] [EC 2.7.7.49]. Purified by solubilising the virus with non-ionic detergent. Lysed virions were adsorbed on DEAE-cellulose or DEAE-Sephadex columns and the enzyme eluted with a salt gradient, then chromatographed on a phosphocellulose column and enzyme activity eluted in a salt gradient. Purified from other viral proteins by affinity chromatography on a pyran-Sepharose column. [Verna Biochim Biophys Acta 473 1 7977 Smith Methods Enzymol 65 560 1980 see commercial catalogues for other transcriptases.]... 

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

Very few self-sufficient viruses have only 60 protein chains in their shells. The satellite viruses do not themselves encode all of the functions required for their replication and are therefore not self-sufficient. The first satellite virus to be discovered, satellite tobacco necrosis virus, which is also one of the smallest known with a diameter of 180 A, has a protein shell of 60 subunits. This virus cannot replicate on its own inside a tobacco cell but needs a helper virus, tobacco necrosis virus, to supply the functions it does not encode. The RNA genome of the satellite virus has only 1120 nucleotides, which code for the viral coat protein of 195 amino acids but no other protein. With this minimal genome the satellite viruses are obligate parasites of the viruses that parasitize cells. 

We have seen in the structure of this simple satellite virus that 60 subunits are sufficient to form a shell around an RNA molecule that codes for the subunit protein, but there is little room for additional genetic information. 

The size of this viral particle is of course larger than that of a virus with only 60 subunits. The diameter of tomato bushy stunt virus is 330 A compared with 180 A for satellite tobacco necrosis virus. The increase in volume of the capsid means that a roughly four times larger RNA molecule can be accommodated. 

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... 

The fact that spherical plant viruses and some small single-stranded RNA animal viruses build their icosahedral shells using essentially similar asymmetric units raises the possibility that they have a common evolutionary ancestor. The folding of the main chain in the protein subunits of these viruses supports this notion. 

One of the most striking results that has emerged from the high-resolution crystallographic studies of these icosahedral viruses is that their coat proteins have the same basic core structure, that of a jelly roll barrel, which was discussed in Chapter 5. This is true of plant, insect, and mammalian viruses. In the case of the picornaviruses, VPl, VP2, and VP3 all have the same jelly roll structure as the subunits of satellite tobacco necrosis virus, tomato bushy stunt virus, and the other T = 3 plant viruses. Not every spherical virus has subunit structures of the jelly roll type. As we will see, the subunits of the RNA bacteriophage, MS2, and those of alphavirus cores have quite different structures, although they do form regular icosahedral shells. 

Since all members of this family of RNA phages have homologous coat proteins, their subunits are expected to have the same three-dimensional structure. It remains to be seen if the MS2 fold is also present in any other unrelated viruses. The fold is so far unique for the MS2 subunit, but similar structures have been observed in other proteins such as the major histocompatibility antigen, HLA, which was discussed in Chapter 15. 

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... 

The circumstances under which water becomes contaminated are as varied as the ways water is taken internally. It is then conceivable that almost any virus could be transmitted through the water route. The increased use of water for recreational purposes increases the incidence of human contact with bodies of water and, consequently, with waterborne viruses and bacteria. The major waterborne viruses among pathogens, and the most likely candidates for water transmission, are the picornaviruses (from pico, meaning very small, and RNA, referring to the presence of nucleic acid). The characteristics of picornaviruses are shown in Table 1. Among the picornaviruses are the enteroviruses (polioviruses, coxsackieviruses. 

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

Virus Any of a large group of submicroscopic agents infeeting plants, animals, and baeteria, and unable to reproduee outside the tissue of the host. A fully formed virus eonsists of nueleie aeid (DNA or RNA) surrounded by a protein, or protein and lipid eoat. 

Retrovirus (Section 28.13) A virus for which the genetic material is RNA rather than DNA. 

FIGURE 1.25 The virus life cycle. Viruses are mobile bits of genetic iuformatiou encapsulated in a protein coat. The genetic material can be either DNA or RNA. Once this genetic material gains entry to its host cell, it takes over the host machinery for macromolecular synthesis and subverts it to the synthesis of viral-specific nucleic acids and proteins. These virus components are then assembled into mature virus particles that are released from the cell. Often, this parasitic cycle of virus infection leads to cell death and disease. 

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. ... 

In addition to viruses, ribosomes 70S were separated from RNA on the column packed with the same support. The yield of both components was quantitative. 

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. 

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