a single nucleotide polymorphism in tetherin promotes retrovirus restriction in vivo单核苷酸多态性在tetherin促进体内逆转录病毒的限制.pdfVIP
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a single nucleotide polymorphism in tetherin promotes retrovirus restriction in vivo单核苷酸多态性在tetherin促进体内逆转录病毒的限制
A Single Nucleotide Polymorphism in Tetherin Promotes Retrovirus Restriction In Vivo 1 1 2 1 3 1,2,4 Bradley S. Barrett , Diana S. Smith , Sam X. Li , Kejun Guo , Kim J. Hasenkrug , Mario L. Santiago * 1 Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America, 2 Department of Microbiology, University of Colorado Denver, Aurora, Colorado, United States of America, 3 Rocky Mountain Laboratories, National Institutes for Allergy and Infectious Diseases, National Institutes of Health (NIH), Hamilton, Montana, United States of America, 4 Department of Immunology, University of Colorado Denver, Aurora, Colorado, United States of America Abstract Tetherin is a membrane protein of unusual topology expressed from rodents to humans that accumulates enveloped virus particles on the surface of infected cells. However, whether this ‘tethering’ activity promotes or restricts retroviral spread during acute retrovirus infection in vivo is controversial. We report here the identification of a single nucleotide polymorphism in the Tetherin gene of NZW/LacJ (NZW) mice that mutated the canonical ATG start site to GTG. Translation of NZW Tetherin from downstream ATGs deleted a conserved dual-tyrosine endosomal sorting motif, resulting in higher cell surface expression and more potent inhibition of Friend retrovirus release compared to C57BL/6 (B6) Tetherin in vitro. Analysis of (B6 6NZW)F1 hybrid mice revealed that increased Tetherin cell surface expression in NZW mice is a recessive trait in vivo. Using a classical genetic backcrossing approach, NZW Tetherin expression strongly correlated with decreased Friend retrovirus
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