Abstract
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 by 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 methods applied to a transmission tree. Applying the donor-recipient regressions to the CD4+ T cell decline and per-parasite pathogenicity did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model approach, however, we find that the heritability of the decline of CD4+ T cells is 25% (95% CI: 9%–40%) assuming neutral evolution of this trait, or 17% (95% CI: 6%–29%) assuming stabilizing selection. The heritability of per-parasite pathogenicity is estimated as 22% (95% CI: 5%–39%) assuming it evolves neutrally, and 17% (95% CI: 4%–29%) for stabilizing selection. Further, we confirm previous studies that established the heritability of the set-point viral load. Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection. Our results suggest that viral genetic factors affect virulence in two ways: indirectly through influencing the set-point viral load, and directly by modulating the per-parasite pathogenicity of the virus.