Abstract
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes albopictus. CHIKV re-emergence is also associated with new clinical complications including severe morbidity and, for the first time, mortality. In this study, we characterized disease progression and host immune responses in adult and aged Rhesus macaques infected with either the recent CHIKV outbreak strain La Reunion (LR) or the West African strain 37997. Our results indicate that following intravenous infection and regardless of the virus used, Rhesus macaques become viremic between days 1–5 post infection. While adult animals are able to control viral infection, aged animals show persistent virus in the spleen. Virus-specific T cell responses in the aged animals were reduced compared to adult animals and the B cell responses were also delayed and reduced in aged animals. Interestingly, regardless of age, T cell and antibody responses were more robust in animals infected with LR compared to 37997 CHIKV strain. Taken together these data suggest that the reduced immune responses in the aged animals promotes long-term virus persistence in CHIKV-LR infected Rhesus monkeys.
Highlights
Chikungunya virus (CHIKV) is a re-emerging member of the Alphavirus genus within the Togaviridae family
We examined CHIKV immunity in adult and aged Rhesus macaques following infection with two different CHIKV strains
Our data support the clinical findings of CHIKV susceptibility in vulnerable populations including the aged and provide mechanistic evidence that an effective immune response directed against the virus is required for preventing persistent CHIKV infection
Summary
Chikungunya virus (CHIKV) is a re-emerging member of the Alphavirus genus within the Togaviridae family. Several outbreaks occurred in India, where over one million cases were reported [5,6]. In 2006, over 200,000 cases were reported on the island of La Reunion [7,8], the most significant aspect of that outbreak being that a single point mutation in the viral envelope glycoprotein allowed the virus to replicate to very high titers in both Aedes (Ae.) albopictus and Ae. aegypti mosquitos, which are widely distributed throughout the world [3,9,10]. Viremic travelers returning from India initiated a local outbreak in Italy through infection of Ae. albopictus mosquitoes [11,12]. CHIKV cases from travelers returning from endemic regions were reported in France and the United States, demonstrating the potential of CHIKV spread to distant locales [13,14]
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