Multiple human immunodeficiency virus type 1 Nef functions contribute to efficient replication in primary human macrophages

Amanda Brown, Shaghayegh Moghaddam, Thomas Kawano, Cecilia Cheng-Mayer

Research output: Contribution to journalArticlepeer-review

Abstract

The human immunodeficiency virus type 1 (HIV-1) Nef protein has been shown to accelerate viral growth kinetics in primary human T-lymphocytes and macrophages; however, the specific function(s) of Nef responsible for this phenotype in macrophages is unknown. To address this issue, mutants of a molecularly cloned macrophage-tropic isolate, HIV-1SF162, were generated expressing single point mutations that abrogate the ability of Nef to interact with cellular kinases or mediate CD4 down-regulation. Infection of primary monocyte-derived macrophages (MDM) with these mutant viruses revealed that residues in the PXXP motif contribute to efficient replication. Interestingly, viruses expressing alleles of Nef defective in CD4 down-modulation activity retain wild-type levels of infectivity in single-round assays but exhibited delayed replication kinetics and grew to lower titres compared to the wild-type virus in MDM. These data suggest that efficient HIV-1 replication is dependent on the ability of Nef to interact with cellular kinases and remove CD4 from the surface of infected macrophages.

Original languageEnglish (US)
Pages (from-to)1463-1469
Number of pages7
JournalJournal of General Virology
Volume85
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Virology

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