sivsm quasispecies adaptation to a new simian hostsivsm准物种适应新猴主人.pdfVIP

SIVsm Quasispecies Adaptation to a New Simian Host 1¤a 1¤b 1 2¤c 2* Linda J. Demma , John M. Logsdon, Jr. , Thomas H. Vanderford , Mark B. Feinberg , Silvija I. Staprans 1 Department of Biology, Emory University, Atlanta, Georgia, United States of America, 2 Departments of Medicine and Microbiology and Immunology, and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America Despite the potential for infectious agents harbored by other species to become emerging human pathogens, little is known about why some agents establish successful cross-species transmission, while others do not. The simian immunodeficiency viruses (SIVs), certain variants of which gave rise to the human HIV-1 and HIV-2 epidemics, have demonstrated tremendous success in infecting new host species, both simian and human. SIVsm from sooty mangabeys appears to have infected humans on several occasions, and was readily transmitted to nonnatural Asian macaque species, providing animal models of AIDS. Here we describe the first in-depth analysis of the tremendous SIVsm quasispecies sequence variation harbored by individual sooty mangabeys, and how this diverse quasispecies adapts to two different host species—new nonnatural rhesus macaque hosts and natural sooty mangabey hosts. Viral adaptation to rhesus macaques was associated with the immediate amplification of a phylogenetically related subset of envelope (env) variants. These variants contained a shorter variable region 1 loop and lacked two specific glycosylation sites, which may be selected for during acute infection. In contrast, transfer of SIVsm to its natural host did not subject