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Cloettapreis_2004_Nr_32

deficiency virus, which naturally infects Old World monkeys, is less susceptible to the TRIM5␣-mediated block. Host cell barriers may largely explain the current distribution of these viruses among human and non-human primate species (Lee, 2004). We have investigated variation in these antiviral proteins (Bleiber, 2004, An, 2004) and identified a significant polymorphism, including the occurrence of nonsynonymous amino acid substitutions in defined protein motifs. This would indicate that these innate defense elements are under significant selective pressure (Sawyer, 2004, Zhang, 2004). A histidine 186 to arginine change in APOBEC3G, frequently identified in individuals of African ancestry, may be associated with more rapid progression of HIV-1 disease (An, 2004). TRIM5␣ variants are, in the in vitro assay used in our laboratory, associated with differences in the degree of permissiveness of CD4 T cells to HIV-1 infection. Exploring differences in expression or function of these antiviral proteins may shed light on the basis of inter-individual or inter-species differences in susceptibility to retroviruses, and possibly other pathogens (Turelli, 2004). Perspectives The various processes described above lead us to the last issue, whe- ther we are witnessing HIV-1-host co-evolution. The best evidence for the influence of human pathogens on natural selection is exemplified by Malaria (Winkler, 2004). This disease became endemic 6000–10000 years ago, coincident with the rise of agriculture (Tishkoff, 2001, Joy, 2003). The selective pressure over 300–500 generations has resulted in adaptive shifts in the allele frequency of several genes with a role in malaria resistance: the X-linked glucose-6-phosphate dehydrogenase (G6PD), the Duffy antigen receptor for chemokines (DARC), and the ␣ and ␤-globin genes (Fortin, 2002). Another suggestive example of population shaping constitutes the FUT2 – fucosyltransferase 2 and resistance to Norovirus infection. FUT2 encodes ␣1,2 fucosyltrans- ferase that produces H type 1 carbohydrate found in the surface of the intestinal epithelium, required for Norovirus binding (Lindesmith, 23

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