AEGiS-15IAC: Infection of placental cells by HIV-1 occurs through a mechanism independent of gp120/gp41 but dependent of the endosomes.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Infection of placental cells by HIV-1 occurs through a mechanism independent of gp120/gp41 but dependent of the endosomes.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1183)

Vidricaire G, Tremblay MJ
Universite Laval, Ste-Foy, Canada

BACKGROUND: Vertical transmission of HIV-1 is a serious public health issue. HIV-1 enters massively in trophoblasts (cells of the placenta) chiefly via endocytosis, a process leading to infection of these cells. The expression of CD4/CXCR4/CCR5 is controversial in trophoblasts suggesting a different receptor usage by HIV-1. Therefore, the course of infection of HIV-1 in trophoblasts appears to be completely different from what is known for CD4+ T lymphocytes. How HIV-1 ultimately infects trophoblasts remains unresolved. This study addresses two ISSUES: i) the requirement of the viral proteins gp120/gp41 for infection, and ii) the relationship between the presence of HIV-1 within the endocytic compartments and infection.

METHODS: wild-type reporter HIV-1 viruses were compared to fusion incompetent gp41 mutant and Env-deficient HIV-1 virions for binding, entry and infection in polarized trophoblasts. Fusion assays were done with wt and Env-deficient viruses bearing VPR-[betalactamase. Finally, viral expression of HIV-1 was tested in trophoblasts transiently transfected with GFP expression vectors coding for wt or mutant Rab proteins. The Rab proteins tested are associated with early or late endosomes and are known to be required for their function.

RESULTS: Env-deficient and gp41 mutant HIV-1 virions entered massively in trophoblastic cells. Surprisingly, this entry was accompanied with viral replication. Moreover, Env- and gp41-mutant HIV-1 particles underwent fusion in trophoblastic cells. While the entry process was not affected by the expression of the Rab proteins tested, infection was significantly modulated. Conclusion for the first time, we show that entry, fusion and infection of HIV-1 in trophoblastic cells are all independent of gp120/gp41. Strikingly, infection of HIV-1 is associated with events occurring within the endocytic compartments. Collectively these date stress a completely novel mode of replication for HIV-1 and underscore the complexity of the biology of this retrovirus. This has great implication on mother-to-child transmission of HIV-1.

Keywords: AEGIS, HIV Envelope Protein gp120, Green Fluorescent Proteins, HIV-1, Endosomes, Receptors, CXCR4, Antigens, CD4, Receptors, CCR5, Virus Replication, CD4-Positive T-Lymphocytes, Virion, Endocytosis, Child, Humans, immunology, virology

040711
TuOrA1183