ACTIVE HHV-6 INFECTION IN THE LYMPH-NODES OF HIV-INFECTED PATIENTS - IN-VITRO EVIDENCE THAT HHV-6 CAN BREAK HIV LATENCY

Studies published previously by this laboratory have demonstrated that patients with AIDS have widely disseminated, active infections with H HV-6 at the time of their death. However, it remains unclear when in t he course of the human immunodeficiency virus (HIV) infection the acti ve HHV-6 infection first appears. To address this question, lymph node biopsies from 10 HIV-infected patients were analyzed for active human herpesvirus 6 (HHV-6) infections by immunohistochemical staining. Eig ht of the biopsies carried the histologic diagnosis of follicular hype rplasia; the other two were characterized as having follicular involut ion with histiocytosis and reactive lymphadenitis. In total, 10 of 10 (100%) of the lymph nodes studied contained cells productively infecte d with HHV-6; in contrast, three lymph nodes with follicular hyperplas ia and four normal lymph nodes from patients not infected with HIV wer e negative for HHV-6 infection. Of special note, the absolute CD4(+) l ymphocyte counts of 75% (6/8) of the HIV-infected individuals included in these studies were >200/mm(3) at the time of their lymph node biop sy. The A variant of HHV-6 was found to be the predominant form of the virus present in the lymph node biopsies from all of these HIV-infect ed patients, and in vitro studies demonstrated that exposure of monocy tic cells carrying latent HIV to HHV-6A resulted in massive upregulati on of HIV replication from latency. Thus, active HHV-6 infections appe ar relatively early in the course of HIV disease, and in vitro studies suggest that the A variant of HHV-6 is capable of breaking HIV latenc y, with the potential for helping to catalyze the progression of HIV i nfection to AIDS.