Human endogenous retrovirus K gag coassembles with HIV-1 gag and reduces the release efficiency and infectivity of HIV-1

Kazuaki Monde, Rafael Contreras-Galindo, Mark H. Kaplan, David M. Markovitz, Akira Ono

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Human endogenous retroviruses (HERVs), which are remnants of ancestral retroviruses integrated into the human genome, are defective in viral replication. Because activation of HERV-K and coexpression of this virus with HIV-1 have been observed during HIV-1 infection, it is conceivable that HERV-K could affect HIV-1 replication, either by competition or by cooperation, in cells expressing both viruses. In this study, we found that the release efficiency of HIV-1 Gag was 3-fold reduced upon overexpression of HERV-KCON Gag. In addition, we observed that in cells expressing Gag proteins of both viruses, HERV-KCON Gag colocalized with HIV-1 Gag at the plasma membrane. Furthermore, HERV-KCON Gag was found to coassemble with HIV-1 Gag, as demonstrated by (i) processing of HERV-KCON Gag by HIV-1 protease in virions, (ii) coimmunoprecipitation of virion-associated HERV-KCON Gag with HIV-1 Gag, and (iii) rescue of a late-domain-defective HERV-KCON Gag by wild-type (WT) HIV-1 Gag. Myristylation-deficient HERV-KCON Gag localized to nuclei, suggesting cryptic nuclear trafficking of HERV-K Gag. Notably, unlike WT HERV-KCONM Gag, HIV-1 Gag failed to rescue myristylation-deficient HERV-KCON Gag to the plasma membrane. Efficient colocalization and coassembly of HIV-1 Gag and HERV-K Gag also required nucleocapsid (NC). These results provide evidence that HIV-1 Gag heteromultimerizes with HERV-K Gag at the plasma membrane, presumably through NC-RNA interaction. Intriguingly, HERV-K Gag overexpression reduced not only HIV-1 release efficiency but also HIV-1 infectivity in a myristylation-and NC-dependent manner. Altogether, these results indicate that Gag proteins of endogenous retroviruses can coassemble with HIV-1 Gag and modulate the late phase of HIV-1 replication.

Original languageEnglish (US)
Pages (from-to)11194-11208
Number of pages15
JournalJournal of virology
Volume86
Issue number20
DOIs
StatePublished - Oct 2012
Externally publishedYes

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