Human Immunotypes Impose Selection on Viral Genotypes Through Viral Epitope Specificity

Area of Science:

• Genetics
• Immunology
• Virology

Background:

• Understanding host-pathogen genetic interactions is vital for interpreting virulence factors.
• This study examines the genetic interplay between human hosts and human immunodeficiency virus (HIV).

Purpose of the Study:

• To test for associations between HIV and host genetics.
• To investigate interactive genetic effects on viral load (VL) in HIV-positive, antiretroviral treatment-naive individuals.

Main Methods:

• Sequencing of HIV genomes to identify amino acid (AA) variants.
• Association analysis of HIV variants, human single nucleotide polymorphisms (SNPs), and HLA alleles with VL using generalized linear models and Bonferroni correction.

Main Results:

• Four HIV variants were significantly associated with VL.
• Twelve HIV variants showed associations with human SNPs, and 46 associations were found between HLA alleles and HIV variants.
• While HIV variants and immunotypes individually correlated with lower VL, their combined analysis showed an opposite effect, supported by epitope binding predictions.

Conclusions:

• The findings highlight the importance of immunotype specificity on viral antigenic determinants.
• The identified genetic interplay underscores the necessity of studying viral and human genetics concurrently.