Sero-Prevalence and Cross-Reactivity of Chikungunya Virus Specific Anti-E2EP3 Antibodies in Arbovirus-Infected Patients.

Chikungunya virus (CHIKV) and clinically-related arboviruses cause large epidemics with serious economic and social impact. As clinical symptoms of CHIKV infections are similar to several flavivirus infections, good detection methods to identify CHIKV infection are desired for improved treatment and clinical management. The strength of anti-E2EP3 antibody responses was explored in a longitudinal study on 38 CHIKV-infected patients. We compared their anti-E2EP3 responses with those of patients infected with non-CHIKV alphaviruses, or flaviviruses. E2EP3 cross-reactive samples from patients infected with non-CHIKV viruses were further analyzed with an in vitro CHIKV neutralization assay. CHIKV-specific anti-E2EP3 antibody responses were detected in 72% to 100% of patients. Serum samples from patients infected with other non-CHIKV alphaviruses were cross-reactive to E2EP3. Interestingly, some of these antibodies demonstrated clearly in vitro CHIKV neutralizing activity. Contrastingly, serum samples from flaviviruses-infected patients showed a low level of cross-reactivity against E2EP3. Using CHIKV E2EP3 as a serology marker not only allows early detection of CHIKV specific antibodies, but would also allow the differentiation between CHIKV infections and flavivirus infections with 93% accuracy, thereby allowing precise acute febrile diagnosis and improving clinical management in regions newly suffering from CHIKV outbreaks including the Americas. Author Summary: Chikungunya virus (CHIKV) causes Chikungunya fever in humans. The symptoms, particularly joint pain, can be severe and long lasting, and outbreaks can have serious socioeconomic impact. CHIKV is a mosquito-borne alphavirus that co-exists geographically with other mosquito-borne flaviviruses such as dengue virus (DENV). This causes difficulties in diagnosis because the symptoms are similar between CHIKV and DENV infections. It is important to differentiate between CHIKV and DENV infections, with good diagnostic methods. In this paper, we found that 72%–100% of CHIKV-infected patients had antibodies that recognized E2EP3, a part of a CHIKV protein. In contrast, a low percentage of flavivirus-infected patients had antibodies that recognized E2EP3. This suggests that testing patients for the presence of E2EP3-recognizing antibodies will aid in diagnostic differentiation between CHIKV and DENV infections. Interestingly, patients infected with non-chikungunya alphaviruses had moderate levels of antibodies that recognized E2EP3. While it was generally known that the alphaviruses have fairly conserved amino acid sequences, it was unknown until now, to what extent the antibodies against non-chikungunya viruses would also recognize E2EP3 from CHIKV. This paper provides insights about the E2EP3-recognizing antibodies from patients with different mosquito-borne viral infections and these insights will inform approaches to diagnostics and vaccination. [ABSTRACT FROM AUTHOR]