HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral...

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• HIV-1 infection requires viral envelope glycoproteins (Env) to bind target cells via CD4 and chemokine receptors (CCR5/CXCR4).
• Primary cells like lymphocytes and macrophages express both CCR5 and CXCR4, unlike T cell lines that typically express only CXCR4.
• Coreceptor utilization and viral tropism are critical factors in HIV-1 pathogenesis and transmission.

Purpose of the Study:

• To propose a comprehensive classification schema for HIV-1 Env phenotypes.
• To differentiate between viral tropism and coreceptor selectivity.
• To highlight the importance of defining Env phenotype for therapeutic and vaccine development.

Main Methods:

• Analysis of viral envelope glycoprotein (Env) interactions with CD4 and chemokine receptors (CCR5/CXCR4).
• Evaluation of viral tropism across different cell types (T cell lines, lymphocytes, macrophages).
• Correlation of coreceptor usage (R5, X4, R5X4) with observed tropism.

Main Results:

• Viral entry and tropism are regulated by specific utilization of CCR5 and CXCR4 pathways, not solely by coreceptor expression.
• HIV-1 Env phenotypes are characterized by distinct combinations of coreceptor use and target cell tropism.
• Env tropism and coreceptor selectivity are related but distinct viral characteristics.

Conclusions:

• A proposed classification schema for HIV-1 Env phenotypes integrates both tropism and coreceptor use.
• Defining Env phenotype is crucial for developing effective entry inhibitors and vaccines.
• Understanding the interplay between tropism and coreceptor selectivity is vital for deciphering HIV-1 pathogenesis and transmission.