Rhesus macaques model human Mayaro virus disease and transmit toAedes aegyptimosquitoes
Abstract
Background
Mayaro virus (MAYV) is a mosquito-borne alphavirus endemic to Latin America that causes fever and arthritis. Unlike the related chikungunya virus, MAYV has not caused widespread, human-amplified epidemics. One possible explanation is that human viremia levels are too low to support transmission to urbanAedes(Stegomyia)aegyptimosquitoes. We used rhesus macaques (RM) to model human-to-Ae. aegyptitransmission and to further expand understanding of their relevance to human MAYV disease.
Methodology/Principal Findings
Twelve RM were inoculated with a genotype D lineage MAYV strain using one of 3 doses: 7 log10plaque forming units (PFU) intravenously (IV), 7 log10PFU subcutaneously (SC), or 3 log10PFU SC. Viremia was measured daily in plasma and RM were euthanized 10- or 12-days post-inoculation (dpi). On 2, 3, 5, and 7 dpi,Ae. aegyptiwere allowed to bloodfeed, incubated for 10 days, then dissected and tested to detect MAYV in tissues and saliva. RM developed infectious MAYV viremias lasting 3 days, peaking 1-2 dpi with titers ranging from 2-6 log10PFU/ml. RM inoculated with 7 log10PFU IV developed significantly higher viremias (area under the curve) than those receiving 3 log10PFU SC. MAYV RNA was detected in muscle, lymphoid, central nervous, and cardiac tissues. RM showed no signs of fever or joint swelling but some developed mild rashes in areas distant from mosquito feeding sites and histologic inflammation was observed in joints and muscles. OnlyAe. aegyptithat fed on viremic RM 2 dpi became infected, with an overall infection rate of 48%. Among all mosquitoes that fed on RM 2 dpi, only 2% (4/217) had infectious MAYV in their saliva, suggesting transmission competence. Despite 11 of 12 RM transmitting MAYV to at least one mosquito, individual RM varied in infectiousness toAe. aegypti,and mosquito cohort infection rates did not correlate with RM viremia levels.
Conclusions/Significance
RM exhibit short-lived MAYV viremias, broad tissue tropism, and mild joint and muscle inflammation, closely resembling human infection. While viremic RM can infectAe. aegypti, the transmission window is narrow and transmission byAe. aegyptiis rare. The combination of a short infectious period in RM and low transmissibility ofAe. aegyptiinfected from RM may help explain the absence of widespread urban MAYV outbreaks.
AUTHOR SUMMARY
Mayaro virus (MAYV) is a mosquito-borne virus found in Latin America that causes fever and joint pain, similar to chikungunya virus (CHIKV). However, unlike CHIKV, MAYV has not led to large outbreaks. One reason may be that levels of MAYV in human blood are too low forAedes aegyptimosquitoes—known for spreading chikungunya, dengue, and Zika—to pick up and transmit the virus in cities. To better understand this, we studied rhesus macaques, a monkey species that serves as a model for how MAYV behaves in people. We tracked virus levels in their blood and tissues and observed mild joint and muscle inflammation, similar to Mayaro fever in people. Although the macaques were able to infect someAe. aegyptimosquitoes, the transmission window was short, and only a few mosquitoes that became infected had virus in their saliva, suggesting transmission competence. This limited ability of urban mosquitoes to spread MAYV may help explain why major outbreaks have not occurred.
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