Abstract
Opioid withdrawal recurs at high rates in opioid use disorder and compromises the immune system. In general, there are two types of opioid withdrawal: abrupt withdrawal (AW) and precipitated withdrawal (PW). In this study, we examined the effect of morphine AW or morphine PW on HIV infection of human blood monocyte-derived macrophages. We observed that both morphine AW and PW enhanced the susceptibility of macrophages to HIV infection. In addition, both AW and PW activated HIV replication in the latently infected myeloid cells (U1 and OM10.1). Investigation of mechanisms responsible for these observations showed that both AW and PW could inhibit the expression of multiple intracellular HIV inhibitory factors, including APOBE3G/F, SAMHD1, MX2, and HIV restriction microRNAs (miR-28, miR-125b, and miR-150) in macrophages. These findings provide additional evidence to support the notion that opioid use compromises the intracellular anti-HIV immunity and facilitates HIV infection and persistence in macrophages.
Highlights
Opioid withdrawal recurs at high rates in opioid use disorder and compromises the immune system [1, 2]
We examined the effect of morphine abrupt withdrawal (AW) or precipitated withdrawal (PW) on TNF-α-induced HIV replication in latently infected cell lines
We examined whether morphine AW or PW inhibits the expression of these HIV restriction mRNAs in macrophages
Summary
Opioid withdrawal recurs at high rates in opioid use disorder and compromises the immune system [1, 2]. While there are very few studies that examine the impact of morphine withdrawal on host immunity and HIV infection, it is known that opiate addiction compromises the immune system and facilitates HIV infection and replication. We showed that heroin use facilities HIV infection of macrophages through inhibiting the expression of the HIV restriction miRNAs [8]. These findings are clinically relevant and significant as macrophages have an important role in HIV infection during all stages of the disease where they act as key target cells and reservoirs, a means to other tissues in the body, and viral transmitters to CD4+ T cells
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