Productive dual infection of human CD4⁺ T lymphocytes by HIV-1 and HHV-6

Abstract

Although infection by HIV-1 (refs 1 and 2) has been implicated as the primary cause of AIDS and related disorders^3,4, cofactorial mechanisms may be involved in the pathogenesis of the disease. For example, several viruses commonly detected in AIDS patients and capable of transactivating the long terminal repeat of HIV-1, such as herpesviruses^5–7, papovaviruses⁷, adenoviruses⁸ and HTLV-I (ref. 9), have been suggested as potential cofactors. Another candidate is human herpesvirus-6 (HHV-6, originally.designated human B-lymphotropic virus)^10–12, which has not only been iden-tified in most patients with AIDS by virus isolation^10,13,14, DNA amplification techniques¹⁵ and serological analysis¹⁶, but is also predominantly tropic and cytopathic in vitro for CD4⁺ T lym-phocytes^17,18. Here we demonstrate that HHV-6 and HIV-1 can productively co-infect individual human CD4⁺ T lymphocytes, resulting in accelerated HIV-1 expression and cellular death. We also present evidence that HHV-6 transactivates the HIV-1 long terminal repeat (LTR). These observations indicate that HHV-6 might contribute directly or indirectly to the depletion of CD4⁺ T cells in AIDS.