Morphine Withdrawal Enhances HIV Infection of Macrophages

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Opioid use disorder is associated with high relapse rates and immune system compromise.
• Opioid withdrawal, whether abrupt (AW) or precipitated (PW), can significantly impact immune function.
• Understanding the effects of opioid withdrawal on HIV infection is crucial for managing co-infections.

Purpose of the Study:

• To investigate the impact of morphine-induced abrupt withdrawal (AW) and precipitated withdrawal (PW) on HIV infection in human macrophages.
• To determine if opioid withdrawal affects HIV replication in latently infected myeloid cells.
• To elucidate the underlying mechanisms by which opioid withdrawal influences HIV susceptibility and replication.

Main Methods:

• Human blood monocyte-derived macrophages were used to study HIV infection.
• Morphine AW and PW models were employed.
• HIV replication in latently infected myeloid cell lines (U1 and OM10.1) was assessed.
• Expression levels of intracellular HIV inhibitory factors and restriction microRNAs were analyzed.

Main Results:

• Both morphine AW and PW enhanced macrophage susceptibility to HIV infection.
• Opioid withdrawal activated HIV replication in latently infected myeloid cells.
• AW and PW inhibited the expression of crucial intracellular anti-HIV factors, including APOBEC3G/F, SAMHD1, MX2, and specific HIV-restricting microRNAs (miR-28, miR-125b, miR-150).

Conclusions:

• Opioid withdrawal compromises intracellular anti-HIV immunity in macrophages.
• Opioid use and subsequent withdrawal facilitate HIV infection and persistence.
• These findings highlight the critical interplay between opioid use, immune function, and HIV pathogenesis.