TY - JOUR
T1 - With differences in acute viremia in simian immunodeficiency virus δnef-infected animals
AU - Janaka, Sanath Kumar
AU - Tavakoli-Tameh, Aidin
AU - Neidermyer, William J.
AU - Serra-Moreno, Ruth
AU - Hoxie, James A.
AU - Desrosiers, Ronald C.
AU - Paul Johnson, R.
AU - Lifson, Jeffrey D.
AU - Wolinsky, Steven M.
AU - Evans, David T.
N1 - Funding Information:
This work, including the efforts of S.K.J., A.T.-T., W.N., W.S.-M., and D.E., was supported by HHS–National Institutes of Health (NIH) grants (AI098485, AI095098, AI121135, and P51OD011106). This study was also supported in part by federal funds from the National Cancer Institute, National Institutes of Health (contract no. HHSN261200800001E to J.D.L.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Publisher Copyright:
© 2018 American Society for Microbiology. All Rights Reserved.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Tetherin (BST-2 or CD317) is an interferon-inducible transmembrane protein that inhibits virus release from infected cells. To determine the extent of sequence variation and the impact of polymorphisms in rhesus macaque tetherin on simian immunodeficiency virus (SIV) infection, tetherin alleles were sequenced from 146 rhesus macaques, including 68 animals infected with wild-Type SIVmac239 and 47 animals infected with SIVmac239δnef. Since Nef is the viral gene product of SIV that counteracts restriction by tetherin, these groups afford a comparison of the effects of tetherin polymorphisms on SIV strains that are, and are not, resistant to tetherin. We identified 15 alleles of rhesus macaque tetherin with dimorphic residues at 9 positions. The relationship between these alleles and plasma viral loads was compared during acute infection, prior to the onset of adaptive immunity. Acute viremia did not differ significantly among the wild-Type SIV-infected animals; however, differences in acute viral loads were associated with polymorphisms in tetherin among the animals infected with SIVδnef. In particular, polymorphisms at positions 43 and 111 (P43 and H111) were associated with lower acute-phase viral loads for SIVδnef infection. These observations reveal extensive polymorphism in rhesus macaque tetherin, maintained perhaps as a consequence of variability in the selective pressure of diverse viral pathogens, and identify tetherin alleles that may have an inherently greater capacity to restrict SIV replication in the absence of Nef. IMPORTANCE As a consequence of ongoing evolutionary conflict with viral pathogens, tetherin has accumulated numerous species-specific differences that represent important barriers to the transmission of viruses between species. This study reveals extensive polymorphism in rhesus macaque tetherin and identifies specific alleles that are associated with lower viral loads during the first few weeks after infection with nef-deleted SIV. These observations suggest that the variable selective pressure of viral pathogens, in addition to driving the diversification of tetherin among species, also operates within certain species to maintain sequence variation in tetherin.
AB - Tetherin (BST-2 or CD317) is an interferon-inducible transmembrane protein that inhibits virus release from infected cells. To determine the extent of sequence variation and the impact of polymorphisms in rhesus macaque tetherin on simian immunodeficiency virus (SIV) infection, tetherin alleles were sequenced from 146 rhesus macaques, including 68 animals infected with wild-Type SIVmac239 and 47 animals infected with SIVmac239δnef. Since Nef is the viral gene product of SIV that counteracts restriction by tetherin, these groups afford a comparison of the effects of tetherin polymorphisms on SIV strains that are, and are not, resistant to tetherin. We identified 15 alleles of rhesus macaque tetherin with dimorphic residues at 9 positions. The relationship between these alleles and plasma viral loads was compared during acute infection, prior to the onset of adaptive immunity. Acute viremia did not differ significantly among the wild-Type SIV-infected animals; however, differences in acute viral loads were associated with polymorphisms in tetherin among the animals infected with SIVδnef. In particular, polymorphisms at positions 43 and 111 (P43 and H111) were associated with lower acute-phase viral loads for SIVδnef infection. These observations reveal extensive polymorphism in rhesus macaque tetherin, maintained perhaps as a consequence of variability in the selective pressure of diverse viral pathogens, and identify tetherin alleles that may have an inherently greater capacity to restrict SIV replication in the absence of Nef. IMPORTANCE As a consequence of ongoing evolutionary conflict with viral pathogens, tetherin has accumulated numerous species-specific differences that represent important barriers to the transmission of viruses between species. This study reveals extensive polymorphism in rhesus macaque tetherin and identifies specific alleles that are associated with lower viral loads during the first few weeks after infection with nef-deleted SIV. These observations suggest that the variable selective pressure of viral pathogens, in addition to driving the diversification of tetherin among species, also operates within certain species to maintain sequence variation in tetherin.
KW - BST-2
KW - HIV/AIDS
KW - Polymorphism
KW - Rhesus macaque
KW - SIV
KW - Tetherin
UR - http://www.scopus.com/inward/record.url?scp=85055617044&partnerID=8YFLogxK
U2 - 10.1128/JVI.00542-18
DO - 10.1128/JVI.00542-18
M3 - Article
C2 - 30135127
AN - SCOPUS:85055617044
VL - 92
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 22
M1 - e00542
ER -