Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program

Karagiannis, Tanya T; Cleary, John P.; Gok, Busra; Henderson, Andrew J.; Martin, Nicholas G.; Yajima, Masanao; Nelson, Elliot C.; Cheng, Christine S.

doi:10.1038/s41467-020-16159-y

Cited by 44 publications

(31 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Worldwide, it is estimated that 80% of injection drug users take opioids, and 17.8% of them are HIV positive ( 4 , 5 ). Epidemiological studies have shown that chronic opioid administration is immunosuppressive, downregulates the antiviral genes, and increases the susceptibility to infections such as tuberculosis and HIV ( 6 – 12 ). The innate and adaptive immune responses act in synchrony against the invading pathogens, and opioids acting through the opioid receptors alter both these responses ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Chronic Morphine Administration Differentially Modulates Viral Reservoirs in a Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaque Model

Acharya

Olwenyi

Thurman

et al. 2021

J Virol

View full text Add to dashboard Cite

HIV persists in cellular reservoirs despite effective combined antiretroviral therapy (cART) and there is viremia flare up upon therapy interruption. Opioids modulate the immune system and suppress antiviral gene responses, which significantly impact people living with HIV (PLWH). However, the effect of opioids on viral reservoir dynamics remain elusive. Herein, we developed a morphine dependent SIVmac251 infected Rhesus macaque (RM) model to study the impact of opioids on HIV reservoirs. RMs on a morphine (or saline control) regimen were infected with SIVmac251. The cART was initiated in approximately half the animals five weeks post-infection, and morphine/saline administration continued until the end of the study. Among the untreated RM, we did not find any difference in plasma/CSF or in cell-associated DNA/RNA viral load in anatomical tissues. On the other hand, within the cART suppressed macaques, there was a reduction in cell-associated DNA load, intact proviral DNA levels, and in inducible SIV reservoir in lymph nodes (LNs) of morphine administered RMs. In distinction to LNs, in the CNS, the size of latent SIV reservoirs was higher in the CD11b+ microglia/macrophages in morphine dependent RMs. These results suggest that in the proposed model, morphine plays a differential role in SIV reservoirs by reducing the CD4+ T-cell reservoir in lymphoid tissues, while increasing the microglia/reservoir size in CNS tissue. The findings from this pre-clinical model will serve as a tool for screening therapeutic strategies to reduce/eliminate HIV reservoirs in opioid dependent PLWH. IMPORTANCE Identification and clearance of HIV reservoirs is a major challenge in achieving a cure for HIV. This is further complicated by co-morbidities that may alter the size of the reservoirs. There is an overlap between the risk factors for HIV and opioid abuse. Opiates have been recognized as prominent co-morbidities in HIV-infected populations. People infected with HIV also abusing opioids have immune modulatory effects and more severe neurological disease. However, the impact of opioid abuse on HIV reservoirs remains unclear. In this study, we used morphine dependent SIVmac251 infected rhesus macaque (RM) model to study the impact of opioids on HIV reservoirs. Our studies suggested that people with HIV who abuse opioids had higher reservoirs in CNS than the lymphoid system. Extrapolating the macaque findings in humans suggests that such differential modulation of HIV reservoirs among people living with HIV abusing opioids could be considered for future HIV cure research efforts.

show abstract

Section: Introductionmentioning

confidence: 99%

Chronic Morphine Administration Differentially Modulates Viral Reservoirs in a Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaque Model

Acharya

Olwenyi

Thurman

et al. 2021

J Virol

View full text Add to dashboard Cite

show abstract

“…Following LPS stimulation, PBMCs from individuals with chronic opioid use, and PMBCs from healthy individuals treated with morphine in vitro demonstrated reduced interferon-stimulated gene and antiviral gene expression compared to untreated healthy control PBMCs. This effect was observed in all identified cell subsets including monocytes, CD4 + T cells, CD8 + T cells, B cells, and NK cells [ 136 ]. Interestingly, morphine treatment of hepatocytes has also been associated with reduced IFN-α production and enhanced HCV replication in vitro [ 137 ].…”

Section: Understanding Vaccine Immunogenicity In Populations Most At Risk For Hcvmentioning

confidence: 99%

Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial

Phelps

Walker

Honegger

2021

Viruses

View full text Add to dashboard Cite

Thirty years after its discovery, the hepatitis C virus (HCV) remains a leading cause of liver disease worldwide. Given that many countries continue to experience high rates of transmission despite the availability of potent antiviral therapies, an effective vaccine is seen as critical for the elimination of HCV. The recent failure of the first vaccine efficacy trial for the prevention of chronic HCV confirmed suspicions that this virus will be a challenging vaccine target. Here, we examine the published data from this first efficacy trial along with the earlier clinical and pre-clinical studies of the vaccine candidate and then discuss three key research directions expected to be important in ongoing and future HCV vaccine development. These include the following: 1. design of novel immunogens that generate immune responses to genetically diverse HCV genotypes and subtypes, 2. strategies to elicit broadly neutralizing antibodies against envelope glycoproteins in addition to cytotoxic and helper T cell responses, and 3. consideration of the unique immunological status of individuals most at risk for HCV infection, including those who inject drugs, in vaccine platform development and early immunogenicity trials.

show abstract

“…Next-generation sequencing technologies such as RNA-sequencing have become standard for querying gene expression in tissues and cells 24 . Gene expression patterns in bioinformatics data sets help provide information about expression differences, relevant clinical features and functions, and clinical outcomes related to these genes.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of expression and prognosis for signal transducer and activator of transcription family in acute myeloid leukemia

Qin¹,

Shao²,

Zhao³

2021

Preprint

View full text Add to dashboard Cite

In recent years, it has become clear that signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. However, the expression level, genetic variation, molecular mechanism, and biological function of different STATs in acute myeloid leukemia (AML) and its relationship with prognosis and immune infiltration in AML have not been fully elucidated. We found that the expression levels of STAT1, STAT2, STAT4, and STAT6 were higher in AML than in normal tissues, whereas the expression levels of STAT3, STAT5A, and STAT5B were lower in the former than in the latter. Survival analysis revealed that high STAT5B level predicted superior OS in these patients. Cox multivariate analysis as well as least absolute shrinkage and selection operator (LASSO) regression screening showed that STAT5B expression is a good independent prognostic factor of OS. The functions of STAT5B are mainly related to the occurrence, development and microenvironment of AML. We also discovered that the expression of STAT5B was significantly correlated with immune infiltrates in AML. In summary, our research demonstrates that STAT5B may be used as a novel predictive biomarker and immunotherapy target for AML patients.

show abstract

Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program

Cited by 44 publications

References 45 publications

Chronic Morphine Administration Differentially Modulates Viral Reservoirs in a Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaque Model

Chronic Morphine Administration Differentially Modulates Viral Reservoirs in a Simian Immunodeficiency Virus SIVmac251-Infected Rhesus Macaque Model

Where to Next? Research Directions after the First Hepatitis C Vaccine Efficacy Trial

Comprehensive analysis of expression and prognosis for signal transducer and activator of transcription family in acute myeloid leukemia

Contact Info

Product

Resources

About