Suppression of CCR5- but not CXCR4-tropic HIV-1 in lymphoid tissue by human herpesvirus 6

Jean Charles Grivel, Yoshinori Ito, Giovanni Fagà, Fabio Santoro, Farida Shaheen, Mauro S. Malnati, Wendy Fitzgerald, Paolo Lusso, Leonid Margolis

Research output: Contribution to journalArticlepeer-review


HIV-1 infects target cells via a receptor complex formed by CD4 and a chemokine receptor, primarily CCR5 or CXCR4 (ref. 1). Commonly, HIV-1 transmission is mediated by CCR5-tropic variants, also designated slow/low, non-syncytia-inducer or macrophage-tropic, which dominate the early stages of HIV-1 infection and frequently persist during the entire course of the disease2-9. In contrast, HIV-1 variants that use CXCR4 are typically detected at the later stages, and are associated with a rapid decline in CD4+ T cells and progression to AIDS (refs. 2,7-11). Disease progression is also associated with the emergence of concurrent infections that may affect the course of HIV disease by unknown mechanisms. A lymphotropic agent frequently reactivated in HIV-infected patients is human herpesvirus 6 (HHV-6), which has been proposed as a cofactor in AIDS progression12. Here we show that in human lymphoid tissue ex vivo13-15, HHV-6 affects HIV-1 infection in a coreceptor-dependent manner, suppressing CCR5-tropic but not CXCR4-tropic HIV-1 replication, as shown with both uncloned viral isolates and isogenic molecular chimeras. Furthermore, we demonstrate that HHV-6 increases the production of the CCR5 ligand RANTES ('regulated upon activation, normal T-cell expressed and secreted'), the most potent HIV-inhibitory CC chemokine16, and that exogenous RANTES mimics the effects of HHV-6 on HIV-1, providing a mechanism for the selective blockade of CCR5-tropic HIV-1. Our data suggest that HHV-6 may profoundly influence the course of HIV-1 infection.

Original languageEnglish
Pages (from-to)1232-1235
Number of pages4
JournalNature Medicine
Issue number11
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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