Opiate use inhibits TLR9 signaling pathway in vivo: possible role in pathogenesis of HIV-1 infection

Abstract

The molecular mechanism of opiate use promoting HIV-1 infection is not fully understood. TLR9 is expressed in many immune cells, including monocytes, macrophages, which can recognize viruses and viral products and consequently induce the production of antiviral factors and initiate immune responses. Previous studies have shown that chronic viral infections can overcome and impair TLR9 pathway. We aimed to explore whether opiate use enhances HIV infection through inhibition of TLR9 pathway via a population-based study. A total of 200 subjects were enrolled and divided into four groups as follows: Opiate+ HIV+ (50), Opiate− HIV+ (50), Opiate+ HIV− (50), and healthy control (Opiate− HIV−, 50). All HIV-infected subjects did not receive antiretroviral therapy while they were enrolled in the study. The results showed that opiate use was associated with higher viral load and lower CD4+ T cell count. Opiate use alone led to lower expression of TLR9, IRF7, and IFN-α at the protein level in PBMCs. Combined with HIV-1 infection, opiate use resulted in lower expression of MyD88, ISG56, and MxA. In addition, morphine treatment promoted HIV-1 replication in macrophages via inhibition of TLR9 pathway. Our data reveal that opiate use plays a cofactor role in pathogenesis of HIV-1 infection through inhibition of TLR9 pathway.

The Prediction of miRNAs in SARS-CoV-2 Genomes: hsa-miR Databases Identify 7 Key miRs Linked to Host Responses and Virus Pathogenicity-Related KEGG Pathways Significant for Comorbidities

“…This KEGG pathway has been related to enhanced HIV-1 infection [30] and morphine treatment has been shown to promote HIV-1 replication in macrophages via inhibition of the TLR9 pathway [64]. Furthermore, an increased rate of HIV-1/HTLV-I infection has been observed due to morphine in injection drug users [65]. Morphine is also associated with enhanced hepatitis C virus (HCV) replicon expression [66,67].…”

Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles

“…The neural pathways involved in opioid enhancement of HIV-induced inflammation and cell death appear to involve the activation of MOP and downstream effects through PI3K/Akt and/or MAPK signal transduction ( Hauser et al, 2005 ). Recent studies by Liao et al (2017) have shown that combined with HIV-1 infection, morphine reduces the expression of MyD88, ISG56, and Mxa in macrophages by inhibiting the TLR9 pathway, which in turn promotes the replication of HIV-1 in macrophages.…”

MicroRNAs for Virus Pathogenicity and Host Responses, Identified in SARS-CoV-2 Genomes, May Play Roles in Viral-Host Co-Evolution in Putative Zoonotic Host Species

“…miR-5197 is critical for mucin-type O-glycan biosynthesis pathways, which relate to both human and veterinary viral infections, including HTLV-1, Ebola, HIV-1, HSV-1, avian influenza, and avian oncogenic retrovirus [ 46 , 47 , 48 , 49 , 50 , 51 ]. miR-5197 is also related to the KEGG morphine addiction pathway, which is linked to enhanced HIV-1 infection, HCV replicon expression, the reduced clearance of pulmonary influenza virus infection in rats, and increased SAIDS in rhesus monkeys [ 52 , 53 , 54 , 55 , 56 , 57 ]. miR-5197 furthermore influences the metabolism of xenobiotics by cytochrome P450 mechanisms and the TGF-β signaling pathway, which is associated with viral entry and HIV infection [ 58 ] and is strongly linked to both pulmonary and cardiovascular diseases [ 59 , 60 , 61 ].…”