Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone.
J Virol
; 89(22): 11176-89, 2015 Nov.
Article
in En
| MEDLINE
| ID: mdl-26223636
ABSTRACT
UNLABELLED Macrophages are a target for infection with HIV and represent one of the viral reservoirs that are relatively resistant to current antiretroviral drugs. Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages. IMPORTANCE Our work demonstrates for the first time the selective concentration of MGBG by monocytes/macrophages, leading to the inhibition of HIV-1 expression and a reduction in proviral load within macrophage cultures. These results suggest that MGBG may be useful in adjunctive macrophage-targeted therapy for HIV infection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenosylmethionine Decarboxylase
/
Virus Replication
/
Monocytes
/
HIV-1
/
Virus Integration
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Anti-Retroviral Agents
/
Macrophages
/
Mitoguazone
Limits:
Humans
Language:
En
Journal:
J Virol
Year:
2015
Type:
Article
Affiliation country:
United States