Serological cross-reactivity among common flaviviruses

Abstract

The Flavivirus genus is made up of viruses that are either mosquito-borne or tick-borne and other viruses transmitted by unknown vectors. Flaviviruses present a significant threat to global health and infect up to 400 million of people annually. As the climate continues to change throughout the world, these viruses have become prominent infections, with increasing number of infections being detected beyond tropical borders. These include dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Several highly conserved epitopes of flaviviruses had been identified and reported to interact with antibodies, which lead to cross-reactivity results. The major interest of this review paper is mainly focused on the serological crossreactivity between DENV serotypes, ZIKV, WNV, and JEV. Direct and molecular techniques are required in the diagnosis of Flavivirus-associated human disease. In this review, the serological assays such as neutralization tests, enzyme-linked immunosorbent assay, hemagglutination-inhibition test, Western blot test, and immunofluorescence test will be discussed. Serological assays that have been developed are able to detect different immunoglobulin isotypes (IgM, IgG, and IgA); however, it is challenging when interpreting the serological results due to the broad antigenic cross-reactivity of antibodies to these viruses. However, the neutralization tests are still considered as the gold standard to differentiate these flaviviruses.

Tick-borne encephalitis virus IgG antibody surveillance: vaccination- and infection-induced seroprevalences, south-western Germany, 2021

“…These viruses are not endemic in Europe and are considered to be travelrelated. While we did not review our participants' vaccination status against YFV and JEV, it is known that these viruses induce of cross-reactive antibodies against TBEV [25]. The rate of other flavivirus vaccinations and/or infections may be higher than observed in this study as the primary inclusion criterion was the presence of TBEV IgG antibodies.…”

Epidemiology, biology, pathogenesis, clinical manifestations, and diagnosis of dengue virus infection, and its trend in Ethiopia: a comprehensive literature review

“…Flavivirus including Zika virus (ZIKV), West Nile virus (WNV), Chikungunya virus (CHIKV), Wesselsbron, Talaguine and Sindbis viruses were serologically identified in human populations and in wild animals in Southern and Western Ethiopia [38]. Despite potential serological cross-reactivity due to the broad antigenic cross-reactivity of antibodies and clinical presentation similarities with causing febrile illness to these Flavivirus infections [39], DENV infection was not identified and reported until the last decade in Ethiopia.…”

Zika Virus looming epidemic in Pakistan: seroprevalence findings by plaque reduction neutralization test in the Sindh Region of Pakistan

“…The PRNT plays an important role in confirming ZIKV infections, as well as in identifying false-positive ZIKV IgM results to rule out ZIKV infection. Previous studies have shown serologic cross-reactivity between ZIKV and related flaviviruses, including DENV, but the degree to which neutralizing antibody cross-reactivity limits the ability to identify the specific virus responsible for the current infection is not clear (29). One published report suggests that relative levels of neutralizing antibody titers can distinguish ZIKV from DENV infections, especially in specimens collected months after infection (30).…”