Evaluation of STAT-activator HODHBt in Modulating HIV-1 Infection of Human Interleukin-34 and Macrophage Colony Stimulating Factor-1 Differentiated Macrophages
Open AccessMacrophages play a dual role in HIV-1 infection -- as a direct target for HIV-1 infection, as well as being involved in the antiviral response against HIV and other viruses. The antiviral response culminates with the activation of the Signal Transducer and Activator of Transcription (STAT) pathway, which allows for the induction of interferon stimulated genes (ISGs) and is a vital part of the primary response to foreign pathogens. 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one (HODHBt) is benzotriazin derivative that has been seen to induce activation of STAT5, as well as STATs 1 and 3, and leads to reactivation of the HIV-1 latent reservoir in CD4+ T cells. In this paper, we characterized the effects of HODHBt treatment on both Macrophage Colony Stimulating Factor-1 (MCSF, CSF-1) and Interleukin-34 (IL34) differentiated macrophages, in order to gain a better understanding of the overall cellular events in response to treatment. We evaluated changes in morphology as well as surface marker expression of key proteins involved in HIV-1 infection and macrophage differentiation. We also looked into the potential of HODHBt as an adjuvant in the antiviral response modulating the STAT1 pathway and how that may alter macrophage susceptibility to HIV infection. We demonstrated that HODHBt treatment upregulates STAT1 expression in both CSF-1 and IL-34 differentiated macrophages, as well as causes a drastic morphological difference by inducing a more elongated shape. We also observed that treatment with HODHBt, after primary HIV-1 infection with an R5 virus, significantly decreased intracellular p24 levels. This is a marker for active viral replication, and suggests that this compound may play a role in potential therapeutic strategies towards mitigating active HIV-1 replication in macrophages.
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Moszczynski_gwu_0075M_15658.pdf | 2022-03-06 | Open Access |
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