Interaction of the host and viral genome and their influence on HIV disease
- 1National Laboratory for HIV Immunology, Public Health Agency of Canada, Canada
- 2Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Canada
The course of Human Immunodeficiency Virus type 1 (HIV) infection is a dynamic interplay in which both host and viral genetic variation, among other factors, influence disease susceptibility and rate of progression. HIV set-point viral load, a key indicator of HIV disease progression, has an estimated 30% of variance attributable to common heritable effects and roughly 70% attributable to environmental factors and/or additional non-genetic factors. Genome-wide genotyping and sequencing studies have allowed for large-scale association testing studying host and viral genetic variants associated with infection and disease progression. Host genomics of HIV infection has been studied predominantly in Caucasian populations consistently identifying human leukocyte antigen (HLA) genes and C-C motif chemokine receptor 5 (CCR5) as key factors of HIV susceptibility and progression. However, these studies don’t fully assess all classes of genetic variation (e.g. very rare polymorphisms, copy number variants etc.) and do not inform on non-European ancestry groups. Additionally, viral sequence variability has been demonstrated to influence disease progression independently of host genetic variation. Viral sequence variation can be attributed to the rapid evolution of the virus within the host due to the selective pressure of the host immune response. As the host immune system responds to the virus, e.g. through recognition of HIV antigens, the virus is able to mitigate this response by evolving HLA-specific escape mutations. Diversity of viral genotypes has also been correlated with moderate to strong effects on CD4+ T cell decline and some studies showing weak to no correlation with set-point viral load. There is evidence to support these viral genetic factors being heritable between individuals and the evolution of these factors having important consequences in the genetic epidemiology of HIV infection on a population level. This review will discuss the host-pathogen interaction of HIV infection, explore the importance of host and viral genetics for a better understanding of pathogenesis and identify opportunities for additional genetic studies.
Keywords: HIV infection, Genetic Variation, set point viral load, genome-wide studies, genetic epidemiology, host-pathogen interaction
Received: 12 Oct 2018;
Accepted: 21 Dec 2018.
Edited by:Ping An, Frederick National Laboratory for Cancer Research (NIH), United States
Reviewed by:Mark Z. Kos, University of Texas Rio Grande Valley Edinburg, United States
Taisuke Izumi, Henry M. Jackson Foundation, United States
Copyright: © 2018 McLaren and Tough. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Paul J. McLaren, National Laboratory for HIV Immunology, Public Health Agency of Canada, Winnipeg, Manitoba, Canada, firstname.lastname@example.org