A TRIM5α-independent post-entry restriction to HIV-1 infection of macaque cells that is dependent on the path of entry

Mario Javier Pineda, Brannon R. Orton, Julie Overbaugh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The replication of human immunodeficiency type-1 (HIV-1) is restricted in macaque cells, in part due to host factors that provide intrinsic immunity after entry. Here we show that a rhesus macaque epithelial cell line engineered to express human CD4, sMAGI cells, has at least two post-entry restrictions to HIV-1 replication: one that is dependent on a previously described post-entry restriction factor of macaque cells, TRIM5α, and another that is primarily TRIM5α-independent. The TRIM5α restriction, which was observed with particles that had an HIV-1 core pseudotyped with VSV-G envelope, is saturable and can be completely abrogated by introducing TRIM5α-specific siRNA into the cells. A similar TRIM5α-dependent restriction was observed when sMAGI cells expressing human CCR5 were infected with an R5-HIV-1. In contrast, even when viruses enter sMAGI cells using CD4 and an endogenous rhesus coreceptor at levels sufficient to saturate TRIM5α, they do not productively infect the sMAGI cells. Nor does treatment of sMAGI cells with TRIM5α-specific siRNA relieve this post-entry restriction; this was true whether the HIV-1 core was pseudotyped with SIV envelope or an R5-HIV-1 envelope. Together these data suggest that there is an alternate restriction to replication, here called Lv3, that is encountered by viruses that enter via interaction with CD4 and an endogenous rhesus coreceptor. Thus, these findings suggest that post-entry events are dependent upon the mechanism by which HIV-1 enters the cell.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalVirology
Volume363
Issue number2
DOIs
StatePublished - Jul 5 2007

Keywords

  • CCR5
  • Coreceptor
  • Entry
  • HIV
  • Macaque cells
  • Post-entry
  • TRIM5α

ASJC Scopus subject areas

  • Virology

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