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Published Date: 2019-11-05 22:27:02
Subject: PRO/AH/EDR> Spondweni virus: teratogenic effects & Aedes aegypti transmission
Archive Number: 20191105.6763938
SPONDWENI VIRUS: TERATOGENIC EFFECTS AND AEDES AEGYPTI TRANSMISSION
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Date: Wed 30 Oct 2019
Source: BioRxiv [edited]
https://www.biorxiv.org/content/10.1101/824466v1.full


Anna S. Jaeger, Andrea M. Weiler, Ryan V. Moriarty, Sierra Rybarczyk, Shelby L. O'Connor, David H. O'Connor, et al. Spondweni virus causes fetal harm in a mouse model of vertical transmission and is transmitted by _Aedes aegypti_ mosquitoes.

Abstract
Spondweni virus (SPONV) is the most closely related known flavivirus to Zika virus (ZIKV). Its pathogenic potential and vector specificity have not been well defined. SPONV has been found predominantly in Africa but was recently detected in a pool of _Culex quinquefasciatus_ mosquitoes in Haiti. Here we show that SPONV can cause significant fetal harm, including demise, comparable to ZIKV, in a mouse model of vertical transmission. Following maternal inoculation, we detected infectious SPONV in placentas and fetuses, along with significant fetal and placental histopathology, together indicating vertical transmission. To test vector competence, we exposed _Aedes aegypti_ and _Culex quinquefasciatus_ mosquitoes to SPONV-infected bloodmeals. _Aedes aegypti_ could efficiently transmit SPONV, whereas _Culex quinquefasciatus_ could not. Our results suggest that SPONV has the same features that made ZIKV a public health risk.

Background
Serological cross-reactivity with ZIKV and other flaviviruses likely still confounds accurate diagnostics today. As a result, only 6 well-documented clinical cases of SPONV infection have ever been described (9-11). It is likely that many infections have gone unrecognized; serosurveys have detected evidence of SPONV infection in 10 countries throughout Sub-Saharan Africa (6,12-15). Still, these 6 cases indicate that infection with SPONV typically involves an acute, self-limiting mild to moderate febrile illness (6), but a subset (4/6) of cases are believed to progress to more serious disease, including vascular leakage and neurological involvement (6,9,10,16,17); these symptoms resemble those of other infections common in the same regions (6,8,18). Nothing is known about the risks posed by SPONV infection during pregnancy in humans.

Potential vectors for SPONV have not been identified, although SPONV has been isolated from several mosquito genera (17,22,23). SPONV is considered to be exclusively mosquito-borne, but recent mouse experiments suggest that it can be sexually transmitted (24). Whether SPONV could spill over into a human-mosquito cycle involving _Aedes aegypti_ is unclear.

Discussion
Together, our data show that SPONV possesses worrisome properties that should prompt further investigation into its epidemic potential and risk to pregnant women. The adaptation of SPONV to an urban or peri-urban cycle, involving _Ae. aegypti_ and/or other mosquitoes in the Stegomyia subgenus (e.g., _Ae. albopictus_) should therefore be a public health concern (47). Given the continuing difficulties in differentiating between flaviviruses in diagnostic assays, understanding SPONV's prevalence in the expanding landscape of cross-reacting, co-endemic mosquito-borne viruses could also be considered a critical public health priority.

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Communicated by:
Mary Marshall
<mjm2020@googlemail.com>

[These results coupled with the isolation of SPONV from mosquitoes collected in Haiti raises some serious public health concerns. SPONV has been reported just once in the Americas (see Spondweni virus - Haiti: 2016, mosquito pool 20180801.5941287). Is it still present in Haiti or other countries in the Americas? Because _Aedes aegypti_ are potential vectors of SPONV, could the virus become established as Zika virus did? Do humans develop a viremia of sufficient amplitude and duration to infect these mosquitoes? As the authors point out, there is likely a diagnostic problem because of cross-reactions with Zika and possibly other flaviviruses. The Spondweni serogroup, in the genus _Flavivirus_ (Flaviviridae), includes 2 species: Spondweni virus (SPONV) and Zika virus (ZIKV). The finding of SPONV in Haiti, in the western hemisphere, is surprising, given that previously it was known only from Africa. Because of the possibility of misdiagnosing SPONV infections clinically as dengue, chikungunya, or especially Zika virus infections in the Americas, SPONV should be included in routine diagnostic tests for patients with febrile illnesses. How SPONV was introduced into Haiti is unknown, as is the extent of its distribution in the Americas.

ProMED-mail thanks Mary Marshall for sending in this report. - Mod.TY]

See Also

2018
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Spondweni virus - Haiti: 2016, mosquito pool 20180801.5941287
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