Viral and cellular requirements for replication of HIV in primary monocytes.
Int Conf AIDS 1991 Jun 16-21; 7:100 (abstract no. M.A.1033) Schuitemaker H, Kootstra NA, Groenink M, Meyaard L, de Goede RE, Huisman H, Miedema F, Tersmette M; Central Lab. Neth. Red Cross Blood Transf. Serv. and Lab. of Exp. and Clin. Immunology of the Univ. of Amsterdam, Amsterdam, The Netherlands
The biological phenotype and the prevalence of monocytotropic HIV-1 isolates was studied by cell-free infection and primary isolation studies on sequential blood samples. In cell-free infection studies on primary monocyte derived macrophages (MDM) with 17 non-syncytium-inducing (NSI) and 14 syncytium-inducing (SI) isolates a correlation between NSI phenotype and tropism for monocytes was demonstrated. These monocytotropic isolates are present at all stages of HIV-1 infection as could be concluded from primary isolation studies. Transient expression in MDM of reporter gene CAT, driven by LTR's derived from distinct HIV-1 variants did not reveal differences. Transfection experiments with full-length infectious, genetically related, molecular clones different for SI capacity and host range indicated restriction at the level of virus entry. Five day treatment with rIL-4, previously described to induce differentiation-like effects in monocytes, prior to infection resulted in the complete absence of HIV-1 expression. IL-4 treatment after infection had no effect. IL-4 did not act by down modulation of CD4 expression nor at the transcriptional level since induction of LTR-driven CAT activity in IL-4 treated monocytes was seen. Concomitant with differentiation, complete inhibition of monocyte proliferation was seen. It appeared that monocyte proliferation is a prerequisite for infection with HIV-1. We conclude that NSI HIV-1 variants are more monocytotropic as compared to SI variants with the level of restriction most likely at entry. Although a certain level of monocyte differentiation seems to be necessary for infection, HIV expression will occur only in macrophages that have been infected before the stage of terminal differentiation.
Keywords: AEGIS, Monocytes, Virus Replication, HIV-1, Macrophages, HIV Infections, Antigens, CD4, Giant Cells, Interleukin-4, Tropism, Terminal Repeat Sequences, Cats, Animal, virology, genetics, ICA7 910616
MA1033
