Eliminating the persistent HIV reservoir based on biomarker expression - How do we get there?

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• The persistent Human Immunodeficiency Virus (HIV) reservoir, characterized by varying proviral transcriptional activity, impedes efforts toward an HIV cure.
• The lack of a definitive molecular signature or biomarker for latently HIV-infected cells hinders effective reservoir eradication strategies.

Purpose of the Study:

• To discuss factors contributing to biomarker heterogeneity in the HIV reservoir.
• To highlight the need for identifying a minimal set of cell surface proteins that collectively define all HIV reservoir subsets.
• To emphasize the importance of characterizing tissue biomarkers and myeloid lineage cells for comprehensive reservoir targeting.

Main Methods:

• Literature review and discussion of factors influencing biomarker heterogeneity.
• Analysis of consistently reported biomarkers like programmed cell death 1 (PD-1) and Fc fragment of IgG low affinity IIa receptor (FcγRIIa).
• Exploration of novel technologies such as spatial transcriptomics and proteomics for future research.

Main Results:

• Biomarker heterogeneity is influenced by external stimuli, tissue microenvironments, and inter-person variability.
• While some biomarkers (e.g., PD-1, FcγRIIa) are consistently reported, they are insufficient alone to identify all reservoir cells.
• A combination of co-expressed proteins is likely necessary to define comprehensive biomarker panels.

Conclusions:

• A minimal set of cell surface proteins is needed to accurately define all HIV reservoir subsets.
• Future research should focus on identifying co-expressed proteins and characterizing myeloid lineage reservoirs.
• Advancements in spatial transcriptomics and proteomics hold promise for developing effective reservoir-targeting strategies for an HIV cure.