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 target cell susceptibility to HIV-1 infection and replication. Although the advent of highly active antiretroviral therapy (HAART) has altered these sequelae, co-infections may prevail in some parts of the world and in failed HAART regimens. Moreover, immune activation as occurs in tonsil and non-infectious mucosal inflammatory lesions may also be associated with proximal sites of viral replication. These connections between enhancement of HIV-1 infection and activation/inflammation warrant further elucidation of the factors promoting permissiveness to HIV-1 infection. Using the opportunistic pathogen Mycobacterium avium as an in vitro model, we demonstrated that co-infection facilitated HIV-1 infection of monocyte-macrophages by multiple pathways. M. avium activated NF-kappaB, the downstream consequences of which included augmented expression of tumor necrosis factor alpha and CCR5 receptors, both permissive for sustaining HIV-1 infection. Pronounced viral replication in lymph nodes co-infected with M. avium and HIV-1 paralleled these in vitro findings. Furthermore, reduction in viral burden is associated with treatment of infected or inflamed tissues, underscoring the link between immune activation and viral replication.
Wahl
S M
SM
National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4352, USA. smwahl@dir.nidcr.nih.gov
Greenwell-Wild
T
T
Hale-Donze
H
H
Moutsopoulos
N
N
Orenstein
J M
JM
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000821:virology*; D015269:Mycobacterium avium Complex; D015270:Mycobacterium avium-intracellulare Infection / Q000150:complications / Q000276:immunology / Q000821:virology; D014779:Virus Replication