About this item:

517 Views | 0 Downloads

Author Notes:

Address correspondence to: Richard W. Compans, Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Room 5005, Atlanta, Georgia 30322. E-mail:rcompan@emory.edu

Subject:

Research Funding:

This study was supported by a grant from the National Institutes of Health (AI090840).

Effects of Stabilization of the gp41 Cytoplasmic Domain on Fusion Activity and Infectivity of SIVmac239

Tools:

Journal Title:

AIDS Research and Human Retroviruses

Volume:

Volume 27, Number 11

Publisher:

, Pages 1213-1222

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Abstract We investigated the effects of introducing specific sequences that are predicted to affect trimer stability into the CT domain of the SIV Env protein. Two constructs, 3HBai and 3HBaa, with additional GCN4-related sequences in the CT domain (45 aa) had enhanced infectivity, and differed in their fusion activity and trimer stability. Another construct, 3HBii, exhibited a very stable trimeric structure. Pseudotyped virions containing 3HBii retained infectivity despite the lack of syncytia formation. In contrast, 3HBai and 3HBaa, which caused extensive syncytia formation, had a less stable trimeric structure. We observed an inverse correlation between trimer stability and fusion activity but no correlation between syncytia formation activity and infectivity. Quantitative cell–cell fusion assays, analysis of Env incorporation, measurement of ectodomain conformation by CD4 binding, and CCR5 blocking assays indicated differential effects on fusion activity and infectivity of the viruses with Env CT modifications. Differences in interaction with CD4 were not affected by trimer stability and were not related to fusion activity or infectivity. The results indicate that changes in the stability of the CT domain can have significant effects on functional activities of the Env external domain and can impact viral biological properties.

Copyright information:

Copyright 2011, Mary Ann Liebert, Inc.

Export to EndNote