adaptation of hiv-1 depends on the host-cell environmenthiv - 1的适应性取决于宿主细胞环境.pdfVIP

Adaptation of HIV-1 Depends on the Host-Cell Environment 1,2¤ 1 2 1 Tim van Opijnen *, Anthony de Ronde , Maarten C. Boerlijst , Ben Berkhout 1 Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2 Section Population Biology, Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands Many viruses have the ability to rapidly develop resistance against antiviral drugs and escape from the host immune system. To which extent the host environment affects this adaptive potential of viruses is largely unknown. Here we show that for HIV- 1, the host-cell environment is key to the adaptive potential of the virus. We performed a large-scale selection experiment with two HIV-1 strains in two different T-cell lines (MT4 and C8166). Over 110 days of culture, both virus strains adapted rapidly to the MT4 T-cell line. In contrast, when cultured on the C8166 T-cell line, the same strains did not show any increase in fitness. By sequence analyses and infections with viruses expressing either yellow or cyan fluorescent protein, we were able to show that the absence of adaptation was linked to a lower recombination rate in the C8166 T-cell line. Our findings suggest that if we can manipulate the host-cellular factors that mediate viral evolution, we may be able to significantly retard viral adaptability. Citation: van Opijnen T, de Ronde A, Boerlijst MC, Berkhout B (2007) Adaptation of HIV-1 Depends on the Host-Cell Environment. PLoS ONE 2(3): e271. doi:10.1371/journal.pone.0000271 INTRODUCTION asexuals (non-recombining individuals) two beneficial mutations Disease progression in HIV-1 infected patients shows extensive have to be fixed sequentially, wherea