# Trade-offs between Arbovirus Transmission and Clearance in Native and Novel Hosts

> **NIH NIH R01** · NEW MEXICO STATE UNIVERSITY LAS CRUCES · 2020 · $825,889

## Abstract

Research Summary
The recent introduction of Zika virus (ZIKV) into the New World sparked concern that the virus would emerge
into a sylvatic cycle in American non-human primates (NHPs) and mosquitoes. The ability of a pathogen to
emerge into a novel host species is determined, in part, by the virulence of that pathogen in the novel species.
Current theory on the evolution of virulence rests on the premise that pathogen fitness is maximized by
optimizing the trade-off between instantaneous pathogen transmissibility and duration of infection. While most
theoretical studies of virulence evolution have focused on the trade-off between transmission and host
mortality, the majority of pathogens do not kill their hosts. Instead, most infections are curtailed by the host
immune response, leading to a transmission-clearance trade-off. Studies of the transmission-clearance
trade-off are scarce, but we have previously found that, across multiple studies in the literature, there is an
inverse relationship between peak virus titer and duration of infection when arthropod-borne viruses are
experimentally inoculated into natural hosts. Moreover, we have leveraged these data to model alternate
transmission strategies, namely a “tortoise” strategy of low magnitude, long duration viremia and a “hare”
strategy of short duration, high magnitude viremia and found that arboviruses that adopted a tortoise strategy
had higher rates of persistence in both host and vector populations. Nonetheless current understanding of
transmission-clearance trade-offs in arboviruses is rudimentary, and integrated experimental and modeling
studies of arbovirus trade-offs in ecologically-relevant host and vector species are needed to appropriately
assess the risk of establishment of sylvatic cycles in new areas and the subsequent risk of emergence from
such cycles. To this end, we will quantify dynamics of ZIKV and dengue virus (DENV) infection, immune
response, and transmission in native NHP hosts (cynomolgus macaques) as well as novel, American NHPs
(squirrel monkeys) to identify transmission-clearance trade-offs, and we will build models to predict the impact
of such trade-offs on virus persistence in host populations. DENV is chosen as a counterpoint to ZIKV
because, despite circulating in humans in the Americas for centuries, it has not yet established an American
sylvatic cycle [17]. We will test four specific hypotheses: (i) In native hosts and novel hosts, sylvatic
arboviruses experience a transmission-clearance trade-off; (ii) In native and novel hosts, the innate immune
response shapes the transmission-clearance trade-off; (iii) Sylvatic arboviruses experience different
transmission-clearance trade-offs in native hosts and novel hosts, resulting in less transmission from novel
hosts; (iv) DENV and ZIKV lineages from human-endemic transmission cycles experience different
transmission-clearance trade-offs than their sylvatic ancestors in native NHP hosts, but similar patterns in
...

## Key facts

- **NIH application ID:** 9971290
- **Project number:** 1R01AI145918-01A1
- **Recipient organization:** NEW MEXICO STATE UNIVERSITY LAS CRUCES
- **Principal Investigator:** Ben Althouse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $825,889
- **Award type:** 1
- **Project period:** 2020-02-24 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971290

## Citation

> US National Institutes of Health, RePORTER application 9971290, Trade-offs between Arbovirus Transmission and Clearance in Native and Novel Hosts (1R01AI145918-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971290. Licensed CC0.

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