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4 - Retroviruses Introduction 1904 Ellerman and Bang...

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Retroviruses Introduction: 1904: Ellerman and Bang, searching for an infectious cause (bacterium) for leukaemia, studied leukaemia in chickens and succeed in transferring the disease from one to another by cell-free tissue filtrates. 1911: Peyton Rous transmitted solid tumours of chickens by transplanting tissue, but also isolated the infectious agent (RSV). This discovery was followed by many other examples of acutely transforming retroviruses, together with the structural characterization of the viruses involved. 1960's: Howard Temin knew that retrovirus genomes were composed of RNA and observed that replication was inhibited by actinomycin D (inhibits DNA synthesis therefore he proposed the concept of reverse transcription (Nobel prize awarded to Baltimore and Temin, 1975). 1969: Huebner and Todaro proposed the viral oncogene hypothesis - the transmission of viral and oncogenic information as genetic elements (rather than as a pathogenic response to a virus) - explains the vertical (germ line) transmission of 'cancers', first observed by Gross, 1951. 1981: Human T-cell leukaemia virus discovered, the first pathogenic human retrovirus. 1983: Human immunodeficiency virus discovered. Most of the retroviruses we currently know (many!) infect vertebrates, but as a group, they have been identified in virtually all organisms including invertebrates - evolutionarily successful design! Taxonomy: Genus: Type Species: Avian type C retroviruses avian leukosis virus (ALV) BLV-HTLV retroviruses bovine leukaemia virus (BLV) Lentivirus human immunodeficiency virus (HIV-1) Mammalian type B retroviruses mouse mammary tumor virus (MMTV) Mammalian type C retroviruses murine leukaemia virus (MLV) Spumavirus human spumavirus (HSRV) Type D retroviruses Mason-Pfizer monkey virus (MPMV)
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Classification by morphology Historically, retroviruses were divided into groups based on their morphology in negatively-stained E.M. pictures: A-type: Also known as 'intracisternal particles'. Non-enveloped, (non-infectious???) immature particles only seen inside cells, believed to result from endogenous retrovirus-like genetic elements. B-type: Enveloped, extracellular particles with a condensed, acentric core and prominent envelope spikes, e.g. MMTV. C-type: As B-type, but with a central core and barely visible spikes - e.g. most mammalian and avian retroviruses (MLV, ALV, HTLV, HIV). D-type: Usually slightly larger (to 120nm) and spikes less prominent, e.g. MPMV. In the era of molecular biology, most comparisons are made on the basis of sequence conservation. Retrovirus Structure: There is considerable diversity between various types of retrovirus; the following is a generalized description of the particle. There is a universal nomenclature for retrovirus proteins: All the above proteins are essential for replication; some retroviruses also encode additional essential and non-essential proteins.
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