Permissive factors for HIV-1 infection of macrophages

Immunodeficiency, the consequence of HIV-1 infection, predisposes the host to opportunistic infections. in turn, opportunistic pathogens influence tar get cell susceptibility to HIV-1 infection and replication. Although the ad vent of highly active antiretroviral therapy (HAART) has altered these sequ elae, co-infections may prevail in some parts of the world and in failed HA ART regimens. Moreover, immune activation as occurs in tonsil and non-infec tions mucosal inflammatory lesions may also be associated with proximal sit es of viral replication. These connections between enhancement of HIV-1 inf ection and activation/inflammation warrant further elucidation of the facto rs promoting permissiveness to HIV-1 infection. Using the opportunistic pat hogen Mycobacterium avium as an in vitro model, we demonstrated that co-inf ection facilitated HIV-1 infection of monocyte-macrophages by multiple path ways. M. avium activated NF-kappa B, the downstream consequences of which i ncluded augmented expression of tumor necrosis factor alpha and CCR5 recept ors, both permissive for sustaining HIV-1 infection. Pronounced viral repli cation in lymph nodes co-infected with M. avium and HIV-1 paralleled these in vitro findings. Furthermore, reduction in viral burden is associated wit h treatment of infected or inflamed tissues, underscoring the link between immune activation and viral replication.