Features of the SIVmac transmembrane glycoprotein cytoplasmic domain that are important for ENV functions

Barbara Shacklett, Caroline Denesvre, Bertrand Boson, Pierre Sonigo

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The cytoplasmic domain (CD) of the SIVmac transmembrane protein (TM) can affect viral infectivity by modulating several Env functions, notably fusogenic capacity and incorporation into virions. In addition, envelopes with a truncated CD are counterselected in primary cells in culture and in vivo in rhesus macaques, suggesting a role for this domain in vital persistence. Here, we have used mutagenesis to examine specific features of the SIVmac TM CD, including the conserved C-terminal α helix and the overall length of the CD. Several mutations dramatically reduced and/or delayed virus infectivity in lymphoid cell lines. Detailed analysis of mutants revealed defects in envelope stability, fusogenic capacity, and virion incorporation. The primary defect associated with an envelope containing a 64-residue CD was rapid degradation. A mutant Env lacking the C-terminal α helix but encoding an exceptionally long CD (373 residues) was highly fusogenic but inefficiently incorporated into virions. A third mutant, containing amino acid substitutions designed to alter the charge density of the C-terminal helix, retained cytopathic properties and showed enhanced fusogenic capacity but replicated with delayed kinetics. Taken together, these results demonstrate that CD sequence variation entails functional 'tradeoffs' that can involve optimization of certain Env functions at the expense of others.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
JournalAIDS Research and Human Retroviruses
Volume14
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

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Virion
Glycoproteins
Primary Cell Culture
Amino Acid Substitution
Macaca mulatta
Mutagenesis
Lymphocytes
Viruses
Cell Line
Mutation
Proteins
Protein Domains

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Features of the SIVmac transmembrane glycoprotein cytoplasmic domain that are important for ENV functions. / Shacklett, Barbara; Denesvre, Caroline; Boson, Bertrand; Sonigo, Pierre.

In: AIDS Research and Human Retroviruses, Vol. 14, No. 5, 20.03.1998, p. 373-383.

Research output: Contribution to journalArticle

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