Differential Contribution of HIV-1 Subtypes B and C to Neurological Disorders: Mechanisms and Possible Treatments

Abstract

With the introduction of combinatory antiretroviral therapy, patients infected with human immunodeficiency virus type 1 (HIV-1) can live much longer than before. However, the identification of HIV-associated neurocognitive disorder (HAND), especially HIV-associated dementia in 15-20% of patients infected with HIV-1, indicates additional complexity. These disorders turn out to be subtype dependent. Recently, many studies are ongoing trying to understand how the virus induces neuronal injury which could lead to neurological dysfunction. Most of these studies are focusing on the HIV-1 release of proteins such as Tat. However, the exact role of these proteins and their involvement in neuronal degeneration remains unidentified; this is especially true since viral proteins from different HIV-1 subtypes differ in their ability to cause neuronal damage. This review describes the role of different HIV-1 subtypes, identifies probable pathways involved in neuronal damage, the contribution of different HIV-1 subtypes to the progression of HAND, and potential treatments for HAND.

Molecular Modeling of Subtype-Specific Tat Protein Signatures to Predict Tat-TAR Interactions That May Be Involved in HIV-Associated Neurocognitive Disorders

“…In contrast, the dominant HIV-1 subtype C (HIV-1C) is responsible for the highest HIV-1 prevalence (>50% of cases) and is present in countries of Southern Africa and India ( Geretti, 2006 ; Shen et al, 2011 ). The neuropathophysiology related to the onset of HAND are different between HIV-1B and HIV-1C ( Tyor et al, 2013 ; Santerre et al, 2019 ). In particular, the subtype-specific differences can be linked to sequence variation within key viral proteins including glycoprotein 120 ( Colon and Vazquez-Santiago, 2015 ), Viral protein R ( Dampier et al, 2017 ), and transactivator of transcription (Tat; Rao et al, 2008 ).…”

Identification of peptide epitopes of the gp120 protein of HIV-1 capable of inducing cellular and humoral immunity

“…126 full sequences for gp120 protein of HIV-1 (from group M subtype B) were found at NCBI (ESI: † Fig. S1), being this subtype B the most predominant in the developed countries of the world, such as the United States and European countries, 30 and also, the most disseminated variant. 31 These protein sequences were submitted to multiple alignment sequence analysis obtaining a consensus sequence ( Fig.…”

The relationship between HIV‐1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post‐mortem brain tissue

“…However, where the mean values were not available, the median values were used. Last, we wanted to determine if HIV subtype variation may have influenced the association between inflammatory markers and NCI/HIVE in post‐mortem brain tissue of PLWH, considering the fact that the HIV‐1 subtype variation and subtype‐specific viral protein amino acid substitutions can influence the prevalence of HAND, 91 , 92 , 93 , 94 as well as the levels of inflammatory markers. 95 , 96 …”

“… 144 Therefore, these findings may reflect the inflammatory profile within the brains of participants with subtype B infection, rather than other geographical subtypes. Considering the significant impact that subtype variance has on the underlying mechanisms of HAND, 92 , 145 as well as clinical neurocognitive impairment in PLWH, 94 , 146 , 147 we suggest that viral subtyping should be included as part of routine analysis in human post‐mortem studies of HIV.…”