Is Sindbis Virus a Risk for Public Health in Israel?

אסנת הלפרן 1,3 Ravit Koren 1 Nataly Avizov 1 Ravit Bassal 2 Tamy Shohat 2,3 Daniel Cohen 3 Laor Orshan 4 Uri Shalom 5 Tomer Israely 6 Nir Paran 6 Sharon Melamed 6 Ella Mendelson 1,3 Yaniv Lustig 1 Tamar Yeger 5
1Central Virology Laboratory, Ministry of Health, Israel
2Israel Center for Disease Control, Ministry of Health, Israel
3Sackler Faculty of Medicine, Tel-Aviv University, Israel
4Laboratory of Entomology, Ministry of Health, Israel
5Environmental Protection, Ministry of Environmental Protection, Israel
6Institute for Biological Research, Israel Institute for Biological Research, Israel

Sindbis virus (SINV) is a mosquito-borne alphavirus with global circulation. SINV disease outbreaks are mainly reported in North European (NE) countries and South Africa. SINV was isolated from mosquitoes in Israel since the 1980s but SINV disease outbreaks have never been recorded.
Our study aims to analyze the risk for SINV infection in Israel. We first assessed SINV circulation in mosquitoes in Israel by analyzing 3008 mosquito pools collected during 2004-6 and 2013-15 which demonstrated that 6.3% (191 pools) of total pools were positive for SINV-RNA and that all sequenced Israeli SINV strains belong to SINV genotype I. We then evaluated the seroprevalence of SINV in the Israeli population by a cross-sectional nationwide serological survey to detect SINV IgG antibodies using 3,145 sera samples. Overall, 3.6% of the serum samples were positive for SINV IgG with higher seroprevalence at ages 65 and above, suggesting that humans in Israel are infected with SINV. To examine the virulence of the Israeli SINV strains, we infected cell lines representing muscle, immune, endothelial and neuronal tissues with either Israeli or NE strains. Our preliminary results demonstrate that the NE SINV strains replicated preferentially in endothelial and neuronal cells while the Israeli SINV replicated better in two B cell lines. Importantly, in vivo infection of 7 day old mice with NE SINV resulted in ~90% mortality but mortality of only ~6% was observed with the Israeli SINV.

Overall our results show that SINV is endemic in mosquitoes and infects humans in Israel without apparent clinical manifestation. Furthermore, in vivo and in vitro experiments suggest that the SINV currently circulating in Israel is less virulent than the NE strains; thus, SINV infection may be primarily subclinical in humans in Israel.









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