PhD thesis and Habilitation

PhD Thesis

Lisboa, 2001

Tropism and infectivity of HIV-2: Study of virus-cell interactions of macrophage-tropic variants

The main objective of the work described in this thesis was to study the virus-cell interactions performed by M-tropic variants of HIV-2, using the primary HIV-2ALI strain as a model.

Summary
In this study, an HIV-2 (HIV-2ALI; shown here interacting with a CD4+ T-lymphocyte), that I isolated from an symptomatic patient was used as a model of HIV-2 interaction with host cells. I deciphered the phenotypic and genotypic features of HIV-2ALI isolate. The main objective of the work described in this thesis was to study the virus-cell interactions performed by M-tropic variants of HIV-2, using the primary HIV-2ALI strain as a model. This virus is unable to productively infect any of the CD4+ cell lines tested. Accordingly viral replication cycle was analysed in order to identify the step responsible for this restricted tropism. The results showed that the abortive infection in those cell lines was due to a block at the level of virus entry into target cells.

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Habilitation

Lisboa 2015

HIV interaction with target cell coreceptors, or why HIV-2 is less virulent than HIV-1

An overview of the mechanisms underlying HIV interaction with co-receptors and how these mechanisms contribute to the minor virulence observed in HIV-2 infection.

During the last decade my group has been devoted to study the mechanisms and pathogenic implications of HIV-2 engagement with cellular coreceptors. We have provided evidence that HIV-1 and HIV-2 interaction with these coreceptors is remarkably different. HIV- 2 isolates that are able to infect cells in the absence of CD4, the promiscuous use of chemokine receptors as coreceptors and the non-usage of either CCR5 or CXCR4 (the main coreceptors used by HIV-1), are notorious examples of the heterogeneous mechanisms by which HIV-2 interacts with and infects target cells.

Different coreceptors usage by HIV-2 and different regions of SU glycoprotein interacting with those coreceptors, should have direct implications in viral replication, in susceptibility to neutralization by host immune response, and to different intracellular signaling resulting altogether in the attenuated infection observed in HIV-2 patients.

So in this Lecture I presented an overview of the mechanisms underlying HIV interaction with coreceptors and how these mechanisms contribute to the minor virulence observed in HIV-2 infection.

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