Dissecting HIV virulence: heritability of setpoint viral load, CD4+ T cell decline and per-parasite pathogenicity. Molecular Biology and Evolution
The ability of pathogens to evoke virulence by different diseases-causing mechanisms independent of their load refers to as ”per-parasite pathogenicity”. Using viral load and CD4+ T cell measures from 2’014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, Bertels at el. aimed to investigate if virulence – measured as the rate of decline of CD4+ T cells – and per-parasite pathogenicity are heritable from donor to recipient. They 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.
They found that 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, the best estimate for the heritability of the CD4+ T cell decline was 17% (5%–30%), and that of the per-parasite pathogenicity was 17% (4%–29%). Further, they confirmed that the set-point viral load is heritable, and estimate a heritability of 29% (12%–46%).
In conclusion, the analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.