Somsen, E. D. | bioRxiv Science

bioRxiv2025

Quantifying viral pandemic potential from experimental transmission studies

In an effort to avert future pandemics, surveillance studies aimed at identifying zoonotic viruses at high risk of spilling over into humans act to monitor the viral chatter at the animal-human interface. These studies are hampered, however, by the diversity of zoonotic viruses and the limited tools available to assess pandemic risk. Methods currently in use include the characterization of candidate viruses using in vitro laboratory assays and experimental transmission studies in animal models. However, transmission experiments yield relatively low-resolution outputs that are not immediately translatable to projections of viral dynamics at the level of a host population. To address this gap, we present an analytical framework to extend the use of measurements from experimental transmission studies to generate more quantitative risk assessments. Specifically, we use within-host viral titer data from index and contact animals to estimate parameters relevant to transmission, including an estimate of transmissibility. We then extended this model to estimate epidemiological parameters, such as the basic reproductive number and generation interval. To illustrate these approaches, we present them in the context of two influenza A virus (IAV) ferret transmission experiments: one using influenza A/California/07/2009 (Cal/2009) and one using influenza A/Hong Kong/1/1968 (Hong Kong/1968). Despite estimating broadly similar transmissibilities for Cal/2009 and Hong Kong/1968, we conclude that Cal/2009 has a higher pandemic potential. This difference in pandemic potential seems to be primarily driven by its more robust within-host replication. Our results critically depend on several assumptions, namely that the within-host viral dynamics in humans and those in the model animal used (here, ferrets) share quantitative similarities and that viral transmissibility between model animals reflects viral transmissibility between humans. The methods we present to assess relative pandemic risk across viral isolates can be used to improve quantitative risk assessment of other emerging viruses of pandemic concern. Author summaryPandemic viruses often originate in animal reservoirs. Surveillance studies at the animal-human interface try to identify which of the many viruses circulating in animals could cause a pandemic in humans. Experimental transmission studies in animal models are one such method used to characterize potential pandemic viruses. However, only simple outcomes usually get reported from these experiments, such as the fraction of animals that become infected in such an experiment. Here, we develop a framework to extract more information from these experiments. Specifically, we use data on the virus population within infected ferrets to extrapolate information about transmission. We then simulate many transmission events to estimate epidemiological parameters commonly used in public health to quantify pandemic potential. Our methods therefore allow us to use commonly gathered data from experimental transmission studies to estimate epidemic dynamics in humans. This set of methods can be used to compare the relative pandemic risk of animal viruses before they emerge in humans.

microbiology↗

bioRxiv2020

Discovery of a novel simian pegivirus in common marmosets (Callithrix jacchus) with lymphocytic enteritis

From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for the presence of RNA viruses. In five out of eight marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus that was not present in ten subsequently deep-sequenced matched, clinically-normal common marmosets with no evidence of lymphocytic enterocolitis. The novel virus, which we have named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A that was previously isolated from a three-striped night monkey (Aotus trivirgatus). To determine the prevalence of this novel virus within the WNPRC marmoset colony, we screened 146 living animals and found an overall prevalence of 34% (50/146). Over the next four years, 85 of the 146 screened marmosets died or were euthanized and were examined histologically for lymphocytic enterocolitis. Out of these 85 animals, 27 SOBV-positive common marmosets had developed lymphocytic enterocolitis, compared to 42 SOBV-negative common marmosets, indicating no evidence of an association between this virus and development of enterocolitis in this cohort (p=0.0798). The novel pegivirus was also found in two of 32 (6%) clinically-normal common marmosets screened while in quarantine during the transfer from the New England Primate Research Center to the WNPRC, suggesting SOBV has different prevalence at different centers and could exert confounding influences on the comparison of marmoset studies from multiple centers. ImportanceCommon marmosets (Callithrix jacchus) are a valuable model species. We discovered two variants of a novel simian pegivirus, which we named the Southwest bike trail virus (SOBV), in common marmosets which had postmortem histologic diagnosis of lymphocytic enterocolitis. The virus was not present in ten matched, clinically-normal controls. We screened 146 live healthy common marmosets in the Wisconsin National Primate Research Center colony and found 34% (50/146) of the animals were SOBV-positive. SOBV was also present in two of 32 (6%) clinically-normal common marmosets from the New England Primate Research Center. These findings could have confounding effects in animal studies, especially those in which infection-free animals are desired, and they demonstrate the need for further investigations into SOBV transmission, the length of time of SOBV persistence, and SOBV prevalence at other primate centers, in order to increase understanding of the effects of SOBV and of this viral genus.

microbiology↗