Morphine stimulates HIV replication in primary cultures of human Kupffer cells

Intravenous drug abusers represent a high risk group for HIV infection in Europe and North America. Although the use of blood-contaminated needles undoubtedly constitutes the main factor of transmission of the virus, an effect of the drug itself either on the immune system or on virus replication, thus favouring the initiation of the infection, may not be excluded. We have formerly established that primary cultures of human Kupffer cells (KC) are permissive for HIV1. In this paper, we describe the effect of morphine hydrochloride on the multiplication of different isolates of HIV1 in cultured human KC. KC were obtained by dissociation of human liver fragments with collagenase and purified by centrifugal elutriation. Five-day-old KC were infected with HIV1; at different intervals, the production of virus was quantitated by the reverse transcriptase activity associated with the particles present in the culture medium. In primary cultures of KC preincubated for 48 h and maintained in the presence of morphine, the production of viral particles was increased. This enhancing effect was found with 3 different HIV1 isolates. Treatment of KC with morphine prior to infection was not required for the stimulation to take place, which indicated that the enhancing effect was not related to a more efficient adsorption of the virus to the KC plasma membrane. Stimulation of HIV1 production was observed for all the concentrations of morphine used (0.05 to 0.5 mg/ml). These results, if confirmed in vivo, may shed new light on the risk factors related to the intravenous administration of heroin.