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The Human Retroviruses
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The retroviruses, which make up a large family (Retroviridae), infect mainly vertebrates. These viruses have a unique replication cycle whereby their genetic information is encoded by RNA rather than DNA. Retroviruses contain an RNA-dependent DNA polymerase (a reverse transcriptase) that directs the synthesis of a DNA form of the viral genome after infection of a host cell. The designation retrovirus denotes that information in the form of RNA is transcribed into DNA in the host cell—a sequence that overturned a central dogma of molecular biology: that information passes unidirectionally from DNA to RNA to protein. The observation that RNA was the source of genetic information in the causative agents of certain animal tumors led to a number of paradigm-shifting biologic insights regarding not only the direction of genetic information passage but also the viral etiology of certain cancers and the concept of oncogenes as normal host genes scavenged and altered by a viral vector.
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The family Retroviridae includes seven subfamilies (Table 196-1). Members of two of the families infect humans with pathologic consequences: the deltaretroviruses, of which human T-cell lymphotropic virus (HTLV) type 1 is the most important in humans; and the lentiviruses, of which HIV is the most important in humans.
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The wide variety of interactions of a retrovirus with its host range from completely benign events (e.g., silent carriage of endogenous retroviral sequences in the germline genome of many animal species) to rapidly fatal infections (e.g., exogenous infection with an oncogenic virus such as Rous sarcoma virus in chickens). The ability of retroviruses to acquire and alter the structure and function of host cell genetic sequences has revolutionized our understanding of molecular carcinogenesis. The viruses can insert into the germline genome of the host cell and behave as a transposable or movable genetic element. They can activate or inactivate genes near the site of integration into the genome. They can rapidly alter their own genome by recombination and mutation under selective environmental stimuli.
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Most human viral diseases occur as a consequence of tissue destruction either directly by the virus itself or indirectly by the host’s response to the virus. Although these mechanisms are operative in retroviral infections, retroviruses have additional mechanisms of inducing disease, including the malignant transformation of an infected cell and the induction of an immunodeficiency state through selective ...