Modulation by complement-opsonized HIV of the initial innate and adaptive defenses – a strategy for the establishment of infection in human cervical and rectal mucosa and immune cells?

The mucosa, which is the port of entry for HIV, comprises several layers of defense, one of which is the complement system.

We need to learn more about the events involved in the initial HIV infection given that the outcome of disease, i.e., rapid or slow progression of AIDS, seems to be determined during the first events and weeks of infection.

During the initial HIV-1 sexual transmission, most virions in the bodily fluids are opsonized, which will influence the outcome of infection. In addition, pre-existing infections, e.g. HSV-2, significantly increase the risk of becoming infected with HIV.

Important immune cells, such as the T cells and dendritic cells (DCs), in HIV-1-infected individuals are dysfunctional on many levels and contribute to HIV pathogenesis.

Our objectives: I) Identify and characterize the pathways and cell subsets that participate in or regulate HIV infection of the mucosa.

II) Elucidate the immunomodulatory effects that complement-opsonized HIV-1, exert on DCs and their abilities to establish infection.

III): Define the pathways and factors responsible for impairment of T cells and DCs when HIV is present during activation of the immune responses. We will use state-of-the-art methods to identify the exact cells and factors instigating the infection.

Determination of contributing factors and cells involved in initiating and establishing the infection is directly relevant to the development of novel HIV preventive treatments and vaccine strategies.