Transcriptomic and Genetic Profiling of HIV-Associated Neurocognitive Disorders.

Daniel Ojeda-Juárez,Marcus Kaul

doi:10.3389/fmolb.2021.721954

Abstract

Early in the HIV pandemic, it became evident that people living with HIV (PLWH) develop a wide range of neurological and neurocognitive complications. Even after the introduction of combination antiretroviral therapy (cART), which dramatically improved survival of PLWH, the overall number of people living with some form of HIV-associated neurocognitive disorders (HAND) seemed to remain unchanged, although the incidence of dementia declined and questions about the incidence and diagnosis of the mildest form of HAND arose. To better understand this complex disease, several transcriptomic analyses have been conducted in autopsy samples, as well as in non-human primates and small animal rodent models. However, genetic studies in the HIV field have mostly focused on the genetic makeup of the immune system. Much less is known about the genetic underpinnings of HAND. Here, we provide a summary of reported transcriptomic and epigenetic changes in HAND, as well as some of the potential genetic underpinnings that have been linked to HAND, and discuss future directions with hurdles to overcome and angles that remain to be explored.

Highlights

Human immunodeficiency virus-1 (HIV-1) is a lentivirus of the Retroviridae family, and it is the causative agent of the acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al, 1983; Gallo et al, 1984; Hahn et al, 1984; Navia et al, 1986a)
The interpretation of the transcriptomic studies is associated with a lot of uncertainty for three major reasons: 1) the variety of criteria and approaches employed for the assessment of HIV-associated neurocognitive impairment (NCI) and HIV-associated neurocognitive disorders (HAND); 2) the overall limited number of cases that were comprehensively characterized for neurocognitive performance and for which corresponding high-quality central nervous system (CNS) RNA is available and, 3) the omission of HIVnegative control subjects in many investigations
To the transcriptomic and epigenetic studies discussed above, the interpretation of the genetic studies, both of candidate genes and genome-wide association studies (GWAS), are hampered by three major issues: 1) the variety of criteria and approaches employed for the assessment of HIV-associated NCI and HAND; 2) the overall limited cases that were comprehensively characterized for neurocognitive performance and for which genomic DNA is available or has been fully sequenced and, 3) the omission of HIV-negative control subjects in many investigations

Summary

Introduction

Human immunodeficiency virus-1 (HIV-1) is a lentivirus of the Retroviridae family, and it is the causative agent of the acquired immunodeficiency syndrome (AIDS) (Barre-Sinoussi et al, 1983; Gallo et al, 1984; Hahn et al, 1984; Navia et al, 1986a). HIV-1 infection remains a serious threat to global health, with around 38 million people living with HIV-1 (PLWH) as of 2020 (Global HIV and AIDS statistics, 2020). In the HIV pandemic before anti-retroviral treatments were available, it became evident that HIV-infection can cause neurological and neurocognitive complications that were referred to as AIDS dementia complex (ADC) and ranged from minor cognitive and motor disorder (MCMD) to full-blown HIV-associated dementia (HAD) (Loewenstein and Sharfstein, 1983; Navia et al, 1986b). At the same time autopsies of many patients who had died from AIDS showed a pronounced neuropathology that is referred to as HIV encephalitis (HIVE) and was often interpreted as the histopathological correlate of ADC, it was noted that not all HAD cases displayed HIVE (Navia et al, 1986a). Several tools were developed to classify the neurological and neurocognitive complications of HIV infection, including the Memorial Sloan Kettering classification of HAD

Methods

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Conclusion