Evaluation of Cross-Protective Responses against Mayaro Virus among Chikungunya Virus-Infected Patients from Paraguay

Mayaro virus (MAYV) is a mosquito-borne alphavirus endemic to Latin America and the Caribbean. It is closely related to chikungunya virus (CHIKV), which has a more global circulation that overlaps with MAYV-endemic areas. Both viruses cause similar symptoms of acute febrile illness and chronic joint pain. Human studies have attempted to determine whether CHIKV can generate cross-protective immunity against MAYV because of their close genetic and antigenic relationship but could not definitively rule out past exposure to MAYV. We investigated cross-reactive MAYV responses using paired blood samples from 15 CHIKV-infected patients from Paraguay, where there have been no reported Mayaro fever cases. These samples were collected during the acute phase of the illness and 2 to 4 weeks after the onset of symptoms. Acute-phase serum samples were confirmed positive for the presence of CHIKV viral RNA with reverse transcription polymerase chain reaction. Plaque reduction neutralization tests were performed on the samples to calculate 80% plaque reduction neutralization titers for CHIKV and MAYV. Previous MAYV exposure was detected in three CHIKV patients, suggesting that past exposure to MAYV might not be sufficient to protect against CHIKV infection. Of the other CHIKV patients without prior MAYV immunity, only one third developed low MAYV cross-neutralizing antibody responses, indicating nonreciprocity in CHIKV and MAYV cross-protection. This study provides evidence of a potential silent circulation of MAYV in Paraguay, which requires further investigation. These findings have critical implications for areas coendemic for MAYV and CHIKV and provide important advances to better understand cross-protection among alphaviruses.