Longitudinal patterns of viremia and oral shedding of rhesus rhadinovirus and retroperitoneal fibromatosis herpesviruses in age-structured captive breeding populations of rhesus Macaques (Macaca mulatta)

Abstract

Rhesus rhadinovirus (RRV) and retroperitoneal fibromatosis herpesvirus (RFHV), 2 closely related γ2 herpesviruses, are endemic in breeding populations of rhesus macaques at our institution. We previously reported significantly different prevalence levels, suggesting the transmission dynamics of RRV and RFHV differ with regard to viral shedding and infectivity. We designed a longitudinal study to further examine the previously observed differences between RRV and RFHV prevalence and the potential influence of age, season, and housing location on the same 90 rhesus macaques previously studied. Virus- and host-genome-specific real-time PCR assays were used to determine viral loads for both RRV and RFHV in blood and saliva samples collected at 6 time points over an 18-mo period. Proportions of positive animals and viral load in blood and saliva were compared between and within viruses by age group, location, and season by using 2-part longitudinal modeling with Bayesian inferences. Our results demonstrate that age and season are significant determinants, with age as the most significant factor analyzed, of viremia and oral shedding for both RRV and RFHV, and these pathogens exhibit distinctly different patterns of viremia and oral shedding over time within a single population.

Figure 1.

Numbers of macaques with repeated positive test results for RRV and RFHV in blood and saliva over all 6 time points. Partial data for animals lost to follow up were included in this graph.

Figure 2.

Proportions (mean ± 1 SD) of macaques with RRV and RFHV in blood and saliva by (A) season and (B) age group from statistical modeling.

Figure 3.

Viral load (mean ± SEM) of RRV and RFHV in (A) blood and (B) saliva from statistical modeling by season.

Figure 4.

Viral load (mean ± SEM) of RRV and RFHV in (A) blood and (B) saliva from statistical modeling by age group.

Figure 5.

Proportions (mean ± 1 SD) of macaques with RRV and RFHV in blood and saliva according to the statistical modeling of the 480 data points collected by corral (A and D, corral 8; B and E, corral 13; C and F, corral 15) and (A–C) season or (D–F) age group.

Figure 6.

Viral load (mean ± SEM) of RRV and RFHV in (A–C) blood or (D–F) saliva according to the statistical modeling of the 480 data points collected by corral (A and D, corral 8; B and E, corral 13; C and F, corral 15) and season.

Figure 7.

Viral load (mean ± SEM) of RRV and RFHV in (A–C) blood or (D–F) saliva according to the statistical modeling of the 480 data points collected by corral (A and D, corral 8; B and E, corral 13; C and F, corral 15) and age group.