Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T Cell Decline and Per-Parasite Pathogenicity

Jacques Fellay, Gabriel Leventhal
2018
Journal paper

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as" per-parasite pathogenicity". Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence - measured as the rate of decline of CD4+ T cells - and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%-30%), and that of the per-parasite pathogenicity is 17% (4%-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.

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Jacques Fellay, Gabriel Leventhal
2018
Journal paper

Abstract

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https://infoscience.epfl.ch/record/233659?ln=en

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Related concepts (10)

Virulence

Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to cause disease—is determined by its virulence factors. In the specific context of gene for gene systems, often in plants, virulence refers to a pathogen's ability to infect a resistant host. The noun virulence derives from the adjective virulent, meaning disease severity.

Directional selection

In population genetics, directional selection, is a mode of negative natural selection in which an extreme phenotype is favored over other phenotypes, causing the allele frequency to shift over time in the direction of that phenotype. Under directional selection, the advantageous allele increases as a consequence of differences in survival and reproduction among different phenotypes. The increases are independent of the dominance of the allele, and even if the allele is recessive, it will eventually become fixed.

Infection

An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection. Infections can be caused by a wide range of pathogens, most prominently bacteria and viruses. Hosts can fight infections using their immune systems. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response.