Toll-like Receptor Response to Human Immunodeficiency Virus Type 1 or Co-Infection with Hepatitis B or C Virus: An Overview

Abstract

Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that play important roles in the early detection of pathogen-associated molecular patterns and shaping innate and adaptive immune responses, which may influence the consequences of infection. Similarly to other viral infections, human immunodeficiency virus type 1 (HIV-1) also modulates the host TLR response; therefore, a proper understanding of the response induced by human HIV-1 or co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), due to the common mode of transmission of these viruses, is essential for understanding HIV-1 pathogenesis during mono- or co-infection with HBV or HCV, as well as for HIV-1 cure strategies. In this review, we discuss the host TLR response during HIV-1 infection and the innate immune evasion mechanisms adopted by HIV-1 for infection establishment. We also examine changes in the host TLR response during HIV-1 co-infection with HBV or HCV; however, this type of study is extremely scarce. Moreover, we discuss studies investigating TLR agonists as latency-reverting agents and immune stimulators towards new strategies for curing HIV. This understanding will help develop a new strategy for curing HIV-1 mono-infection or co-infection with HBV or HCV.

Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review

“…These cells can either promote infection upon TLR engagement or produce proinflammatory cytokines and chemokines to aid in removing the virus. By generating antimicrobial molecules like TNF-α and IFN, PAMP/microbe-associated molecular patterns (MAMPs)-induced activation of TLR signaling reduces the replication and spread of invading pathogens/microbes ( 38 , 39 ). When HBV infection occurs, the TLR response may alter HBV-specific T and B cell responses, ending the HBV infection ( 23 , 40 ).…”

TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview

“…These agonists have gained significant attention as potent immunomodulators capable of inducing the production of IFN, proinflammatory cytokines, and chemokines. They show promise against various viral infections, including HBV, HCV, HIV-1, influenza virus, and SARS-CoV-2 ( Martinsen et al, 2020 ; Kayesh et al, 2021a , c , 2022 , 2023 ; Jimenez-Leon et al, 2023 ; Yin et al, 2023 ). However, further studies are needed to identify potential TLR agonists for vaccine adjuvants.…”

“…HIV/HBV co-infection may lead to increased morbidity and mortality compared to HBV or HIV mono-infection ( Whitaker et al, 2012 ; Kayesh et al, 2023 ). Although the immunogenicity of HBV vaccines is impaired in HIV-infected patients ( de Vries-Sluijs et al, 2020 ), immunization with a HBV vaccine is the most effective way to prevent infection in people with HIV.…”

The ISG15-Protease USP18 Is a Pleiotropic Enhancer of HIV-1 Replication

“…They are potentially recognized by cytoplasmic DNA sensors, such as cyclic GMP–AMP synthase (cGAS), interferon gamma inducible protein 16 (IFI16), and DEAD-box helicase 41 (DDX41), which all lead to the activation of the stimulator of interferon genes (STING)-dependent antiviral immune responses [ 7 , 8 , 9 , 10 , 11 ]. In the event that HIV-1 is taken up by endosomes, the ssRNA genome of HIV-1 can be sensed by endosomal Toll-like receptors (TLRs) [ 12 , 13 ]. After integration, the expressed, unspliced, intron-containing HIV-1 RNA is sensed by RIG-I-like receptors (RLRs) and can induce type I interferon and proinflammatory cytokines ( Figure 1 ) [ 14 , 15 ].…”