Interaction of the Host and Viral Genome and Their Influence on HIV Disease

Abstract

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 (spVL), 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 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 spVL. 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.

Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets

“…The interaction of viruses and host factors has been well documented in the literature [10,[40][41][42][43][44]. Recently, we have started to expand upon our understanding of host-virus interactions to include non-coding RNAs [21,[45][46][47].…”

Network-Based Analysis of OMICs Data to Understand the HIV–Host Interaction

“…The high mutation rate of the HIV genome is one of the reasons for the formation of multiple HIV variants, which have new antigen properties that allow the virus to escape from an immune response (Rogozin et al, 2005;Cuevas et al, 2015). However, polymorphisms in the human genome can also influence the susceptibility to and severity of HIV infections (Le Clerc et al, 2019;Tough and McLaren, 2019). The candidate gene studies revealed a 32-bp deletion in the CCR5 gene (CCR5-32) encoding a co-receptor that is essential for 12 http://www.rna-society.org/virbase/index.html 13 http://210.46.85.180:8080/vmireg 14 http://crdd.osdd.net/servers/virmirna HIV binding to CD4+ cells.…”

New Knowledge About CCR5, HIV Infection, and Disease Progression: Is “Old” Still Valuable?

“…1,2 Several HLA genes or haplotypes appear to influence disease progression, although the effects are complex and may depend on interactions with other host and viral genes. 3 Before the discovery of the role of C-C chemokine receptor (CCR) gene polymorphism in HIV infection and disease progression, only genes of the HLA system were thought to influence HIV disease progression. In the 1990s, studies confirmed the protective role of homozygosity for a 32-bp deletion in CCR5 open reading frame (ORF, CCR5 D32) against HIV infection.…”

“…In the 1990s, studies confirmed the protective role of homozygosity for a 32-bp deletion in CCR5 open reading frame (ORF, CCR5 D32) against HIV infection. [1][2][3] The CCR5 D32 allele is predominantly found in European populations, with no or rare occurrences in Asians and native populations from Africa, the Americas, and Oceania. 4 The presence of one copy of the deleted CCR5 gene also influences the course of disease, as the onset of AIDS occurs later for some heterozygous persons than for those homozygous for the wild-type (wt) CCR5 gene.…”

“…4 The presence of one copy of the deleted CCR5 gene also influences the course of disease, as the onset of AIDS occurs later for some heterozygous persons than for those homozygous for the wild-type (wt) CCR5 gene. [1][2][3] The discovery of the role of CCR5 alleles has prompted studies of the possible role of many other host genes in HIV infection and disease progression. [5][6][7] described hereunder) carriage could be determined, showed that another SNP rs4317138T/C was the top SNP associated with spVL ( p = 7.7 • 10 -22 ).…”