Difference between revisions of "Retroviridae"

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(Reproduction Cycle of a Retroviridae in a Host Cell)
(Viral Ecology & Pathology)
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==Viral Ecology & Pathology==
==Viral Ecology & Pathology==
The pathogenesis of retrovirus has been concentrated on oncogenesis and more recently AIDS but retroviruses cause a variety of haematopoetic and neurological conditions. Some such conditions caused by retroviridae are paralysis, wasting, ataxia, arthritis, dementia and neuropathy.
[http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/index.htm ICTVdB Descriptions]
[http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/index.htm ICTVdB Descriptions]

Revision as of 13:26, 20 June 2006

Baltimore Classification

Higher order taxa

Viruses; Retro-transcribing viruses; Reoviridae


Alpharetrovirus, Betaretrovirus, Spumavirus (examples)

Description and Significance

Genome Structure

The genome of retroviridae is dimeric, unsegmented and contains a single molecule of linear. The genome is -RT and a positive-sense, single-stranded RNA. Minor species of non-genomic nucleic acid are also found in virions. The encapsidated nucleic acid is mainly of genomic origin but virions may also contain nucleic acid of host origin, including host RNA and fragments of host DNA believed to be incidental inclusions. The complete genome of one monomer is 700-11000 nucleotides long. The 5'-end of the genome has a methylated nucleotide cap with a cap sequence type 1 m7G5ppp5'GmpNp. The 3'-terminus of each monomer has a poly (A) tract and the terminus has a tRNA-like structure. (source: ICTVdB Descriptions)

Virion Structure of a Retroviridae

The virions of a retroviridae consist of an encelope, a nucleocapsid and a nucleoid. The virus capsid is enveloped. The virions are spherical to pleomorphic and measure 80-100 nm in diameter. The surface projections are small or distinctive glycoprotein spikes that cover the surface evenly. The projections are densely dispersed and 8 nm long. The nucleoid is concentric or eccentric while the core is spherical. (source: ICTVdB Descriptions)

Reproduction Cycle of a Retroviridae in a Host Cell

The SU envelope glycoprotein binds to a specific receptor on the surface of the host targer cell to initiate the infection. The specificity of this interaction does much to determine the cell-tropism and pathogenesis of different retroviruses and even different isolates of the same virus. Murine reroviruses (MLVs) are sub-divided to three categories on the basis of receptor-determined host species specificity: ecotropic, xenotropic, and amphotropic. Ecotropic MLVs infect only mouse cells, xenotropic MLVs infect only non-mouse cells like rat and hamster, and amphotropic MLVs infect both mouse and non-mouse cells.

Interference between an exogenous virus and an endogenous virus of the same receptor specificity results in interference groups of viruses, as exemplified by ALVs. A number of retrovirus receptor molecules have been identified in recent years.

There is a possibility that receptor binding results in conformational changes in the glycoprotein spike, revealing the fusion domain in the TM protein and resulting in the fusion of the virus envelope with the cell membrane. Very little is known about penetration and uncoating but it is known that uncoating is only partial. resulting eventually in a core particle within the cytoplasm. Reverse transcription occurs inside the ordered structure of this core particle. Reverse transcription is initiated but cannot be completed with the reactants free in solution, and aborts soon after.

The d/s DNA product formed is known as provirus and differs from the vRNA in being longer by one U3,R,U5 sequence. There is a direct repear of this sequence present at each end of the provirus genome as a result, and these are known as the long terminal repeats (LTRs)Three forms of provirus DNA are found in all infected cells.

Integration is a highly specific reaction with respect to the provirus, but random with respect to the host cell DNA. It is believed that the linear form, probably the direct product of reverse transcription, is the substrate used.

The ends of the LTRs consist of inverted repeats of 4-6 bp. These are brought together to form a cleavage site for IN and are cleaved to form a staggered cut. This molecule is then inserted into the host cell DNA. The final results of the integration process is that the integrated provirus contains 1 or 2 less bases at the end of each LTR, the ends of the integrated LTRs always have the same sequence 5' - TG...CA - 3', and 4-6 bp of host cell DNA flanking the integrated provirus are duplicated.

These observations can be explained by a model where a staggered cut (5' overhang) is introduced into both the ends of the LTRs and the host cell DNA, followed by joining of the cut ends and repair of the free 3' ends. The provirus is present for the lifetime of the cell once it is integrated. There is no specific mechanism for the excision of the provirus and the infected cell cannot be cured.

The celllular transcriptional machinery is used by retroviruses for expression, although a few encode additional transcriptional and post-transcriptional regulatory factors - HTLV and HIV. They are therefore expressed like cellular genes. They make use of a number to 'tricks', such as splicing and ribosomal frameshifting to compress maximal information into a small genome.

Various LTRs have been intensively studied and dissected by molecular techniques in recent years. Some of these studies have been related to nucleotide sequencing and comparison with cellular promoter elements with known functions, nuclease protection studies, S1 protection to determine precise transcription start sites - DNAse I protection to determine DNA-binding protein sites in vitro transcription studies.

Splicing is regulated by the cellular apparatus which interacts with cis-acting sequences present in the mRNA. The proteins encoded by gag, pol and pro genes are expressed from a full length genomic RNA, vRNA. TIn complex retros like HTLV and Lentiviruses, multiply spliced mRNAs are produced. The patern of splicing in HIV is very complex.

Pro overlaps gag and/or pol, but is still expressed from the same full-length mRNA. Different viruses have a variety of post-transcriptional stratergies to do this.

Viral Ecology & Pathology

The pathogenesis of retrovirus has been concentrated on oncogenesis and more recently AIDS but retroviruses cause a variety of haematopoetic and neurological conditions. Some such conditions caused by retroviridae are paralysis, wasting, ataxia, arthritis, dementia and neuropathy.


ICTVdB Descriptions