Increased replication of HIV-1 at sites of Mycobacterium tuberculosis infection: potential mechanisms of viral activation.
Tuberculosis (TB) enhances HIV-1 replication and the progression to AIDS in dually infected patients. We employed pleural TB as a model to understand the interaction of the host with HIV-1 during active TB, at sites of Mycobacterium tuberculosis (MTB) infection. HIV-1 replication was enhanced both in the cellular (pleural compared with blood mononuclear cells) and acellular (pleural fluid compared with plasma) compartments of the pleural space. Several potential mechanisms for expansion of HIV-1 in situ were found, including augmentation in expression of tumor necrosis factor (TNF)-alpha and the HIV-1 noninhibitory beta-chemokine (MCP-1), low presence of HIV-1 inhibitory beta-chemokines (MIP-1 alpha, MIP-1 beta, and RANTES [regulated on activation, normal T expressed and secreted]), and upregulation in expression of the HIV-1 coreceptor, CCR5, by pleural fluid mononuclear cells. Thus, at sites of MTB infection, conditions are propitious both for transcriptional activation of HIV-1 in latently infected mononuclear cells, and facilitation of viral infection of newly recruited cells. These mechanisms may contribute to enhanced viral burden and dissemination during TB infection.
Toossi
Z
Z
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland and Veterans Administration Medical Center, Cleveland, Ohio, USA. zxt2@po.cwru.edu
Johnson
J L
JL
Kanost
R A
RA
Wu
M
M
Luzze
H
H
Peters
P
P
Okwera
A
A
Joloba
M
M
Mugyenyi
P
P
Mugerwa
R D
RD
Aung
H
H
Ellner
J J
JJ
Hirsch
C S
CS
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000821:virology*; D001483:Base Sequence; D018925:Chemokines / Q000378:metabolism; D017931:DNA Primers; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014396:Tuberculosis, Pleural / Q000150:complications / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019562:Viral Load; D014775:Virus Activation; D014779:Virus Replication
D018925:Chemokines; D017931:DNA Primers; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha