The Interplay of HIV and Autophagy in Early Infection.

Romina Cabrera-Rodríguez,Daniel Márquez-Arce,Cecilia Cabrera,Silvia Pérez-Yanes,Agustín Valenzuela-Fernández,Judith Estévez-Herrera,Julià Blanco,Lucile Espert

doi:10.3389/fmicb.2021.661446

Abstract

HIV/AIDS is still a global threat despite the notable efforts made by the scientific and health communities to understand viral infection, to design new drugs or to improve existing ones, as well as to develop advanced therapies and vaccine designs for functional cure and viral eradication. The identification and analysis of HIV-1 positive individuals that naturally control viral replication in the absence of antiretroviral treatment has provided clues about cellular processes that could interact with viral proteins and RNA and define subsequent viral replication and clinical progression. This is the case of autophagy, a degradative process that not only maintains cell homeostasis by recycling misfolded/old cellular elements to obtain nutrients, but is also relevant in the innate and adaptive immunity against viruses, such as HIV-1. Several studies suggest that early steps of HIV-1 infection, such as virus binding to CD4 or membrane fusion, allow the virus to modulate autophagy pathways preparing cells to be permissive for viral infection. Confirming this interplay, strategies based on autophagy modulation are able to inhibit early steps of HIV-1 infection. Moreover, autophagy dysregulation in late steps of the HIV-1 replication cycle may promote autophagic cell-death of CD4+ T cells or control of HIV-1 latency, likely contributing to disease progression and HIV persistence in infected individuals. In this scenario, understanding the molecular mechanisms underlying HIV/autophagy interplay may contribute to the development of new strategies to control HIV-1 replication. Therefore, the aim of this review is to summarize the knowledge of the interplay between autophagy and the early events of HIV-1 infection, and how autophagy modulation could impair or benefit HIV-1 infection and persistence, impacting viral pathogenesis, immune control of viral replication, and clinical progression of HIV-1 infected patients.

Highlights

A General Overview of HIVFactors Related to the Control of the Infection and PathogenesisAccording to the Global Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) statistics report published in 2020 by UNAIDS (2020), there were around 38 million people living with HIV and 1.7 million new cases in 2019, and about 26 million people had access to the antiretroviral therapy (ART) at the end of June 2020
Promising results have been obtained with pre-exposure prophylaxis (PrEP) strategies, which aim to prevent both HIV1 infection and transmission and are highly dependent on patient adherence (Straubinger et al, 2019), or by using broadly neutralizing antibodies that could achieve prolonged viral suppression by directly targeting different epitopes from key viral proteins and activating the immune response in order to remove Ab-targeted infected cells (Carrillo et al, 2018; Kumar et al, 2018; Grobben et al, 2019)
It is necessary to study the cellular events triggered by HIV-1 infection and to identify the factors implicated in the control of early HIV-1 infection in order to design valid therapies or vaccines

Summary

Introduction

A General Overview of HIVFactors Related to the Control of the Infection and PathogenesisAccording to the Global Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) statistics report published in 2020 by UNAIDS (2020), there were around 38 million people living with HIV and 1.7 million new cases in 2019, and about 26 million people had access to the antiretroviral therapy (ART) at the end of June 2020. Due to active ART and associated medical achievements, the scientific community considers HIV/AIDS a chronic disease, mainly when access to effective care is assured (Forsyth and Valdiserri, 2012; McGrath et al, 2014). As HIV patients need long-term medication, metabolic concerns, tissue damage and associated aging emerge as a challenge for new drugs and ART regimes (Chawla et al, 2018; Gu et al, 2020). Promising results have been obtained with pre-exposure prophylaxis (PrEP) strategies, which aim to prevent both HIV1 infection and transmission and are highly dependent on patient adherence (Straubinger et al, 2019), or by using broadly neutralizing antibodies (bnAbs) that could achieve prolonged viral suppression by directly targeting different epitopes from key viral proteins and activating the immune response in order to remove Ab-targeted infected cells (Carrillo et al, 2018; Kumar et al, 2018; Grobben et al, 2019)

Objectives

Conclusion