Synthetic Opioid Use and Common Injection-associated Viruses: Expanding the Translational Research Agenda

Blackard, Jason T.; Brown, Jennifer L.; Lyons, Michael S.

doi:10.2174/1570162x17666190618154534

Cited by 4 publications

(4 citation statements)

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“…Nonetheless, it is not known how synthetic opioids may impact viral replication and pathogenesis. As reviewed elsewhere, several distinct opioids promote HIV replication in immune cells [ 19 ]. Potential mechanisms include enhanced chemokine receptor expression, inhibition of β chemokines, antagonism of innate antiviral responses, and altered microRNA (miRNA) expression.…”

Section: Discussionmentioning

confidence: 99%

“…An association between HIV infection and fentanyl use has been reported in several settings [ 17 , 18 ]. Drugs of abuse are known to promote viral replication and virus-mediated pathology (reviewed in [ 8 , 19 ]). Nonetheless, to date, there are no published reports on the effects of fentanyl, fentanyl analogs, or fentanyl metabolites on virus replication despite their widespread recreational use.…”

Section: Introductionmentioning

confidence: 99%

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The synthetic opioid fentanyl enhances viral replication in vitro

et al. 2021

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The US is in the midst of a major drug epidemic fueled in large part by the widespread recreational use of synthetic opioids such as fentanyl. Persons with opioid use disorder are at significant risk for transmission of injection-associated infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). Commonly abused substances may antagonize immune responses and promote viral replication. However, the impact of synthetic opioids on virus replication has not been well explored. Thus, we evaluated the impact of fentanyl and carfentanil using in vitro systems that replicate infectious viruses. Fentanyl was used in cell lines replicating HBV or HCV at concentrations of 1 ng, 100 ng, and 10 ug. Viral protein synthesis was quantified by ELISA, while apoptosis and cell death were measured by M30 or MTT assays, respectively. HCV replicative fitness was evaluated in a luciferase-based system. RNAseq was performed to evaluate cellular gene regulation in the presence of fentanyl. Low dose fentanyl had no impact on HCV replication in Huh7.5JFH1 hepatocytes; however, higher doses significantly enhanced HCV replication. Similarly, a dose-dependent increase in HCV replicative fitness was observed in the presence of fentanyl. In the HepG2.2.15 hepatocyte cell line, fentanyl caused a dose-dependent increase in HBV replication, although only a higher doses than for HCV. Addition of fentanyl resulted in significant apoptosis in both hepatocyte cell lines. Cell death was minimal at low drug concentrations. RNAseq identified a number of hepatocyte genes that were differentially regulated by fentanyl, including those related to apoptosis, the antiviral / interferon response, chemokine signaling, and NFκB signaling. Collectively, these data suggest that synthetic opioids promote viral replication but may have distinct effects depending on the drug dose and the viral target. As higher viral loads are associated with pathogenesis and virus transmission, additional research is essential to an enhanced understanding of opioid-virus pathogenesis and for the development of new and optimized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The synthetic opioid fentanyl enhances viral replication in vitro

et al. 2021

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“…Compared with heroin, fentanyl has a rapid onset but shorter duration of action, which increases the frequency with which people inject drugs and increases drug sharing. Injection drug use increases the risk of transmission of blood-borne viruses such as HIV, hepatitis C virus, and hepatitis B virus [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Viruses 2023, 15, 1027 2 of 19 with CXCR4, including immune system disorders, viral infections, and cancer [18]. Amphetamines, cocaine, marijuana, and opiates are all cofactors that increase the risk of HIV infection and disease progression [19,20].…”

Section: Introductionmentioning

confidence: 99%

The Synthetic Opioid Fentanyl Increases HIV Replication and Chemokine Co-Receptor Expression in Lymphocyte Cell Lines

Krishnan

Kong

Karns

et al. 2023

Viruses

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Background: In the United States, the illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis. Synthetic opioids are known to enhance viral replication and to suppress immunologic responses, but their effects on HIV pathogenesis remain unclear. Thus, we examined the impact of fentanyl on HIV-susceptible and HIV-infected cell types. Methods: TZM-bl and HIV-infected lymphocyte cells were incubated with fentanyl at varying concentrations. Expression levels of the CXCR4 and CCR5 chemokine receptors and HIV p24 antigen were quantified with ELISA. HIV proviral DNA was quantified using SYBR RT-PCR. Cell viability was detected with the MTT assay. RNAseq was performed to characterize cellular gene regulation in the presence of fentanyl. Results: Fentanyl enhanced expression of both chemokine receptor levels in a dose-dependent manner in HIV-susceptible and infected cell lines. Similarly, fentanyl induced viral expression in HIV-exposed TZM-bl cells and in HIV-infected lymphocyte cell lines. Multiple genes associated with apoptosis, antiviral/interferon response, chemokine signaling, and NFκB signaling were differentially regulated. Conclusions: Synthetic opioid fentanyl impacts HIV replication and chemokine co-receptor expression. Increased virus levels suggest that opioid use may increase the likelihood of transmission and accelerate disease progression.

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