AEGiS-11IAC: Differential course of HIV-1 infection in primary human monocytes and macrophages.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Differential course of HIV-1 infection in primary human monocytes and macrophages.

Int Conf AIDS 1996 Jul 7-12; 11:56 (abstract no. Mo.A.1004)
Schneider J, Bohuschke M, Kary B, Herchenroder O; Abt. Virologie, Freiburg, Germany. Fax: *49761 2036639. E- mail: schf@sun1.ukl.uni-freiburg.de.

OBJECTIVE: Blood monocytes can transport HIV from the blood into the organs. As a prerequisite to understand their potential role in the AIDS pathogenesis, we have studied the course of HIV-infection during differentiation of blood monocytes (MO) to adherent macrophages (MF) in vitro.

METHODS: MO from 34 healthy blood donors were purified by ficoll gradient centrifugation, countercurrent elutriation, and 2 hrs adherence. The purified cell populations consisted of more than 98% MO, which differentiated to MF within 6 days of adherent culturing in medium containing 10% of human serum. MO were infected with a low MOI of the macrophage-tropic HIV-1BaL strain at the day of isolation or six days later after differentiation to MF. Virus production was measured in the culture fluids by a commercial HIV-p24 ELISA. Proviral DNA and Virus RNA were detected by nested PCR.

RESULTS: All cultures infected as MF produced virus within 5 days. In contrast infection of MO resulted in spontaneous virus production only in cultures from 34% of the donors. In another 19% of infected MO cultures, virus production could be induced by TNF-alpha and GM-CSF. MO cultures of 47% of the donors remained virus-negative despite this stimulation. Full-length HIV DNA was detected in all cultures after the fourth day of infection, whereas viral RNA was found only in the virus producing cultures.

CONCLUSIONS: Monocytes of all donors were infected. However, in freshly isolated MO from the majority of donors virus replication is inhibited at the level of transcription. This block is not apparent in differentiated MF, and not regularly released during differentiation of MO to MF. The observed variation of virus replication in monocytes of individual donors may contribute to understanding of the individual variations in HIV-induced pathogenesis and should therefore be studied in more detail.

Keywords: AEGIS, Monocytes, Macrophages, HIV Infections, HIV, Virus Replication, HIV Core Protein p24, Acquired Immunodeficiency Syndrome, RNA, Viral, HIV Antibodies, Tumor Necrosis Factor, HIV Antigens, Granulocyte-Macrophage Colony-Stimulating Factor, HIV-1 Reverse Transcriptase, HIV Long Terminal Repeat, HIV Seronegativity, Human, In Vitro, virology, genetics, immunology, ICA11

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MoA1004