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Updated: Apr 7, 2026

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
Published on: November 3, 2014
LncRNA TLR8-AS1 Restricts HIV-1 Infection and Inflammation in Macrophages by Suppressing Arachidonic Acid Metabolism
Fengyi Wang1,2, Shengrui Luo1,2, Junhan Zhang1,2
1Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Background:
Long non-coding RNA (lncRNA) TLR8-AS1 has been implicated in immune regulation, but its role in HIV-1 infection remains unexplored.
Methods:
TLR8-AS1 expression was assessed in PBMCs and primary monocyte-derived macrophages (MDMs) from HIV-1/AIDS patients and healthy controls. Its subcellular localization was determined via bioinformatics, FISH, and nucleocytoplasmic fractionation. In THP-1-derived macrophages, the functional impact of TLR8-AS1 was evaluated using TLR8-AS1 overexpression and NFAT1-knockdown models; viral replication, inflammatory cytokines, and arachidonic acid (AA) metabolism were analyzed by qPCR, ELISA, and Western blot.
Results:
TLR8-AS1 expression levels were positively correlated with CD4+ T cell counts (r=0.439, P < 0.05), suggesting a potential association with immune status. In THP-1-derived macrophages, TLR8-AS1 overexpression significantly inhibited HIV-1 p24 production, viral gene (Pol, Vif, Nef, LTR, and Gag) expression, and secretion of IL-1β, TNF-α, and AA. Mechanistically, cytoplasmic TLR8-AS1 downregulated NFAT1 and PTGS2 (COX-2) expression, selectively suppressing the prostaglandin pathway while leaving the lipoxygenase branch (ALOX5, ALOX15) unaffected. NFAT1 knockdown reproduced the antiviral and anti-inflammatory effects of TLR8-AS1, confirming NFAT1 as a key downstream mediator. In contrast, TLR8-AS1 did not alter TLR8 or its downstream signaling molecules (MyD88 and IRF7), suggesting a TLR8-independent mechanism.
Conclusion:
TLR8-AS1 restricts HIV-1-induced inflammation and viral replication through the NFAT1-AA axis. These findings identify TLR8-AS1 as a potential therapeutic target for mitigating chronic inflammation and viral persistence in HIV-1 infection.
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