Electronic Poster | Session 1
052 – Human Pegivirus-1 exacerbates the neuroinflammatory response in patients co-infected with HIV
Matthew Doan (1) – William Branton (2) – Tom Hobman (3) – Benjamin Gelman (4) – Christopher Power (2)
University of Alberta, Neuroscience and Mental Health Institute, Edmonton, Canada (1) – University of Alberta, Department of Medicine, Edmonton, Canada (2) – University of Alberta, Department of Cell Biology, Edmonton, Canada (3) – University of Texas Medical Branch, Department of Pathology, Galveston, United States (4)
Human pegivirus-1 (HPgV-1) is a positive sense, single-stranded RNA virus of the Flaviviridae family. Several viruses in this family, including Zika and West Nile viruses, have been associated with encephalitis and neuroinflammation. Recently, our group reported HPgV-1 infection in the brains of two patients with fatal leukoencephalitis, wherein HPgV-1 antigen (NS5A) was detected chiefly in glial cells (astrocytes and oligodendrocytes) in cerebral white matter (Balcom, Doan et al., 2018). Interestingly, previous studies have shown that HPgV-1 can be beneficial for patients co-infected with Human Immunodeficiency Virus (HIV). Compared to patients with HIV alone, co-infected patients show higher CD4+ counts, lower plasma HIV viral load, and increased survival. As the central nervous system (CNS) is an important reservoir for HIV and HIV causes a range of neurological symptoms in HIV-infected patients known as HIV-associated neurocognitive disorder (HAND), we hypothesized that HIV and HPgV-1 may likewise interact within the CNS. In this study, we aimed to define the neuroinflammatory profile of HPgV-1 infection both alone and in combination with HIV co-infection, and to delineate the effects of co-infection on viral load in the CNS compartment. To study the in vivo neuroinflammatory effects of HPgV-1 infection, we identified 10 patients with HPgV-1 brain infection (1000-10,000 HPgV-1 RNA copies/g of tissue) in a cohort including HIV-1+ patients, along with age-matched uninfected controls. The expression of proinflammatory cytokine genes (IL1B, TNFA, IL6) was significantly increased in the prefrontal cortex of co-infected patients (n=5) compared to uninfected (n=6) or mono-infected (HIV, n=5; HPgV-1, n=5) patients. In addition, several genes associated with pro-inflammatory regulated cell death (eg. pyroptosis) were elevated in patients co-infected with both viruses, compared to mono-infected patients. Furthermore, HIV viral copy number in the brain, detected by droplet digital PCR (ddPCR), were increased in co-infected patients compared to patients with HIV alone. The present studies indicate that HPgV-1 is a neurotropic virus with the capacity to increase HIV burden in the brain and act synergistically with HIV to promote neuroinflammation in vivo.