From: Jackie Medina
Date: 07 Sep 2003
Time: 20:52:54 -0400
Remote Name: 10.4.7.6
Jackie Medina 9-8-03 BIO 475-01 Report # 1 HOW DOES HIV CAUSE AIDS? Is Genetic Variation Important in Pathogenesis and What is HIV Tropism? In How Does HIV Cause AIDS, Robin A. Weiss attempts to answer how HIV plays a role in the development of AIDS. There are questions like, is HIV sufficient to cause AIDS? Is AIDS an autoimmune disease? In this critique, the focus will be on is genetic variation important in pathogenesis and what is HIV tropism? Weiss believes that genetic variation of HIV may help in pathogenesis. There can be many different subtypes of lentiviruses, slow progressing diseases, within an infected host and are called quasi-species (Meyerhans, et al., 1989). According to Weiss, there are three reasons that HIV could contribute to pathogenesis (Weiss 1993). The first reason is that HIV tropism to different cell types will lead to differences in syndrome attributes, such as immune deficiency and wasting. Secondly, antigenic variation can lead to escape from immune controls (Weiss 1993). Lastly, the rigorousness and rate of the disease can be affected by difference in virulence of strains. However, the genomes are uniform before seroconversion, due to selection for the fastest growing viruses (McNeary, et al., 1992). It is not known yet whether variation is random, driven by immune escape, or driven by acclimatization to cell types. What is known is that variation is traced back to reverse transcriptase, which has no mechanism for catching errors (Meyerhans, et al., 1989). Recombination may allow for mutations to be selected for, which in turn allows for rapid change of the genome (Weiss 1993). Resistance to the cells immune system can be a consequence of this rapid change. The next question Weiss attempts to answer is what is HIV tropism? This stems from the variation of HIV. Weiss states that different strains will differ in their responses, or tropism, to cell types (Weiss 1993). HIV subtypes from the central nervous system (CNS) are macrophage-tropic and those from the peripheral blood lymphocytes (PBL) are T cell-tropic (Levy, 1993). Still there is no common understanding of HIV tropism. Evidence Weiss provides from other sources is first, that the difference in efficiency of HIV replication in T lymphocytes and macrophages is broad (Gendelman, et al., 1990). Second, only a small amount of HIV isolates grow in T- cell lines in the laboratory, whereas nearly all strains, including macrophage-tropic strains grow in PBL. Those isolates in persons without symptoms replicate slowly, but those from AIDS patients replicate much faster (Fenyo, et al., 1988). Finally, there is classification of HIV strains into syncytium-inducing (SI) and non-syncytium-inducing (NSI) isolates. SI isolates are more frequently acquired from AIDS patients (Tersmette, et al., 1989). It is not known if SI viruses cause or are a consequence of immune suppression, but they intensify AIDS once they are the majority in the infected host (Weiss 1993). The use of animal models of lentiviruses, such as visna-maedi disease in mice, may shed light on viral tropism and pathogenesis (Mosier, et al., 1993). To conclude, in this article, Weiss tried to answer many questions pertaining to HIV’s involvement in AIDS development. The role of genetic variation and tropism was part of the focus of the paper. Weiss used knowledge based on his own work and the work of others to shed some light on these two topics. At the time of this article, Weiss was not able to fully answer these questions. Hopefully, they have been answered and further research was and is able to be done. REFERENCES Fenyo, E.M., L. Merfeldt-Manson, F. Chiodi, B. Lind, A. von Gegerfelt, J. Albert, E. Olaussen, and B. Asjo. 1988. Distinctive replicative and cytopathic characteristics of HIV isolates. J. Virol. 62: 4414-9. Gendelman, H.E., L.M. Baca, H. Husayni, J.A. Turpin, D. Skillman, D.C. Kalter, J.M. Orenstein, D.L. Hoover, and M.S. Meltzer. 1990. Macrophage-HIV interaction: viral isolation and target cell tropism. AIDS. 4: 221-8. Levy, J.A. 1993. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 57:193-289. McNearny, T., Z. Hornickova, R. Markham, A. Birdwell, M. Arens, A. Saah, L. Ratner. 1992. Relationship of human immunodeficiency virus type-1 sequence heterogeneity to stage of disease. Proc Natl Acad Sci USA. 89:10247-51. Meyerhans, A., R. Cheynier, J. Albert, M. Seth, S. Kwok, J. Sninsky, L. Merfeldt-Manson, B. Asjo, and S. Wain-Hobson. 1989. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 58:901-10. Mosier, D.E., R.J. Gulizia, P.D. MacIsaac, B.E. Torbett, and J.A. Levy. 1993. Rapid loss of CD4-T cells in human-PBL-SCID mice by nocytopathic HIV isolates. Science. 260: 689-92. Tersmette, M., R.A. Bruters, F. deWolf, R.E. deGoede, J.M. Lange, P.T. Schellekens, J. Gousdsmit, H.G. Huisman, and F. Miedema. 1989. Evidence for role of virulent HIV variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J. Virol. 63: 2118-25. Weiss, R.A. 1993. How Does HIV Cause AIDS? Science. 260:1273-79.
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