TY - JOUR
T1 - Tetherin Antagonism by HIV-1 Group M Nef Proteins
AU - Arias, Juan
AU - Colomer-Lluch, Marta
AU - Bredow, Benjamin von
AU - Greene, Justin
AU - MacDonald, Julie
AU - O'Connor, David
AU - Serra Moreno, Ruth
AU - Evans, David T
N1 - Funding Information:
We thank Stuart Neil, King's College School of Medicine, for providing the Jurkat-TAg L-tetherin and Jurkat-TAg S-tetherin cell lines and Reiko Nishihara, Dana-Farber Cancer Institute, for her guidance with the statistical methods used for this study. We also thank Kim L. Weisgrau and Eva G. Rakasz, Wisconsin National Primate Research Center, for flow cytometry services. D.T.E. is an Elizabeth Glaser Scientist of the Elizabeth Glaser Pediatric AIDS Foundation. This work was supported by National Institutes of Health grants AI098485, AI095098, AI121135, and P51OD011106. This work, including the efforts of Juan F. Arias, Marta Colomer-Lluch, Benjamin von Bredow, Julie MacDonald, Ruth Serra-Moreno, and David T. Evans, was funded by HHS | National Institutes of Health (NIH) (AI098485). This work, including the efforts of David T. Evans, was funded by HHS | National Institutes of Health (NIH) (AI095098). This work, including the efforts of David T. Evans, was funded by HHS | National Institutes of Health (NIH) (AI121135). This work, including the efforts of Justin M. Greene, David H. O'Connor, and David T. Evans, was funded by HHS | National Institutes of Health (NIH) (P51OD011106).
Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016/9/21
Y1 - 2016/9/21
N2 - Although Nef is the viral gene product used by most simian immunodeficiency viruses to overcome restriction by tetherin, this activity was acquired by the Vpu protein of HIV-1 group M due to the absence of sequences in human tetherin that confer sus- ceptibility to Nef. Thus, it is widely accepted that HIV-1 group M uses Vpu instead of Nef to counteract tetherin. Challenging this paradigm, we identified Nef alleles of HIV-1 group M isolates with significant activity against human tetherin. These Nef pro- teins promoted virus release and tetherin downmodulation from the cell surface and, in the context of vpu-deleted HIV-1 recom- binants, enhanced virus replication and resistance to antibody-dependent cell-mediated cytotoxicity (ADCC). Further analysis revealed that the Vpu proteins from several of these viruses lack antitetherin activity, suggesting that under certain circum- stances, HIV-1 group M Nef may acquire the ability to counteract tetherin to compensate for the loss of this f
AB - Although Nef is the viral gene product used by most simian immunodeficiency viruses to overcome restriction by tetherin, this activity was acquired by the Vpu protein of HIV-1 group M due to the absence of sequences in human tetherin that confer sus- ceptibility to Nef. Thus, it is widely accepted that HIV-1 group M uses Vpu instead of Nef to counteract tetherin. Challenging this paradigm, we identified Nef alleles of HIV-1 group M isolates with significant activity against human tetherin. These Nef pro- teins promoted virus release and tetherin downmodulation from the cell surface and, in the context of vpu-deleted HIV-1 recom- binants, enhanced virus replication and resistance to antibody-dependent cell-mediated cytotoxicity (ADCC). Further analysis revealed that the Vpu proteins from several of these viruses lack antitetherin activity, suggesting that under certain circum- stances, HIV-1 group M Nef may acquire the ability to counteract tetherin to compensate for the loss of this f
UR - http://www.scopus.com/inward/record.url?scp=85000932387&partnerID=8YFLogxK
U2 - 10.1128/JVI.01465-16
DO - 10.1128/JVI.01465-16
M3 - Article
VL - 90
SP - 10701
EP - 10714
JO - Journal of Virology
JF - Journal of Virology
IS - 23
ER -