AEGiS-11IAC: Differential growth of HIV-1 subtypes in Langerhans' cells. Relation to transmission route.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Differential growth of HIV-1 subtypes in Langerhans' cells. Relation to transmission route.

Int Conf AIDS 1996 Jul 7-12; 11:224 (abstract no. Tu.A.370)
Soto-Ramirez LE, Renjifo B, Marlink R, McLane MF, Essex M; Harvard School of Public Health, Boston, MA, USA. Fax: (617) 739-8348.

HIV-1 subtype B predominates in the AIDS cases of the US and Europe in infections transmitted through homosexual contact or intravenous drug injection. Conversely the heterosexual AIDS epidemics of Africa and Asia are associated with non-B subtypes. HIV-1 infection with E subtype in Thailand and C in India have rapidly expanded and overcome the initial B epidemics. For heterosexual contact, Langerhans' cells (LC) have been proposed as a possible primary target for HIV-1 infection. Our objective was to compare the ability of HIV-1 isolates from different subtypes to grow in LC.

METHODS: Epidermal LC extracted from healthy human skin through a discontinuous ficoll-metrizoate density gradient were challenged with 9 subtype B primary isolates from US homosexual men, and 18 primary isolates from Asian heterosexually infected people, 16 subtype E from Thailand, and 2 subtype C from India. Virus' replication was assessed in LC and control peripheral blood mononuclear cells(PBMC) by determination of p24 levels in the culture supernatant on days 7,14, and 21.

RESULTS: HIV-1 replication in epidermal suspensions with 90% average of LC was statistically higher at all tested times (p is less than or equal to 0.001 U-Mann Whitney) for Asian viruses, without differences between Thai and Indian isolates. Contrasting, all isolates replicated efficiently in PBMC, with no significant differences seen between US and Asian isolates. No cytophatic effect was seen in LC cultures. LC tropism was independent of macrophage-tropism and of MT-2 cell growth and syncitia formation.

CONCLUSIONS: 1.- HIV-1 subtype E and C isolates replicate in LC at significantly higher levels than does subtype B viruses. 2.- This distinctive LC tropism could explain the differences in frequency of heterosexual transmission of different subtypes of HIV-1 and the major differences seen in the epidemics of Asia and Africa as opposed to those of the US and Europe. 3.- These findings support a possible role of LC as a primary target for heterosexual infection. 4.- Vaccines intended for use in Asia or Africa should be designed to account for these differences.

Keywords: AEGIS, HIV-1, Langerhans Cells, HIV Infections, Acquired Immunodeficiency Syndrome, Heterosexuality, Virus Replication, Growth, Skin, Macrophages, Tropism, Asia, Africa, Europe, India, United States, Thailand, Human, Male, transmission, growth & development, virology, ICA11

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TuA370