DETERMINATION OF AGE-RELATED DEFECTS IN CHIKUNGUNYA VIRUS INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to elucidate the immunological basis of increased susceptibility of aged individuals to Chikungunya virus (CHIKV) infection using a non-human primate (NHP) model. CHIKV, a NIAID Category C Biological Agent, is a re-emerging arbovirus that caused massive recent outbreaks in the Indian Ocean. To date, infections have been limited to Africa and the Indian Ocean Region; however, recent outbreaks in Europe have increased worldwide awareness of this debilitating and potentially lethal viral infection. Importantly, the mosquitoes that transmit CHIKV are now found in much of the Southeastern United States making CHIKV spread possible in the US. While CHIK is not considered to be life threatening, over 200 fatalities were associated with the disease on the French island of Reunion in the Indian Ocean in 2005-6. Additionally, virus-induced arthritis can be extremely debilitating and last for weeks to years in the aged. Severe cases involving infections of the central nervous system have also been described in immune compromised individuals including the elderly. We propose to compare the pathophysiology of CHIKV infection and identify age-related differences in adaptive immunity that underlie increased disease severity in the elderly using a NHP model of CHIKV infection. To date we have performed an initial study to identify the virus strain and dosage that are required for infection of adult Rhesus macaques. We have characterized the immune response and viral load in these animals. We will next infect aged Rhesus macaques.