Restriction of Zika Virus Infection and Transmission in Aedes Aegypti Mediated by an Insect-specific Flavivirus

Overview

Journal Emerg Microbes Infect

Specialty Infectious Diseases

Date 2018 Nov 16

PMID 30429457

Citations 56

Authors

Hannah Romo

Joan L Kenney

Bradley J Blitvich

Aaron C Brault

Affiliations

Soon will be listed here.

Abstract

Previous studies demonstrated an insect-specific flavivirus, Nhumirim virus (NHUV), can suppress growth of West Nile virus (WNV) and decrease transmission rates in NHUV/WNV co-inoculated Culex quinquefasciatus. To assess whether NHUV might interfere with transmission of other medically important flaviviruses, the ability of NHUV to suppress viral growth of Zika virus (ZIKV) and dengue-2 virus (DENV-2) was assessed in Aedes albopictus cells. Significant reductions in ZIKV (100,000-fold) and DENV-2 (10,000-fold) were observed in either cells concurrently inoculated with NHUV or pre-inoculated with NHUV. In contrast, only a transient 10-fold titer reduction was observed with an alphavirus, chikungunya virus. Additionally, restricted in vitro mosquito growth of ZIKV was associated with lowered levels of intracellular ZIKV RNA in NHUV co-inoculated cultures. To assess whether NHUV could modulate vector competence for ZIKV, NHUV-inoculated Aedes aegypti were orally exposed to ZIKV. NHUV-inoculated mosquitoes demonstrated significantly lower ZIKV infection rates (18%) compared to NHUV unexposed mosquitoes (51%) (p < 0.002). Similarly, lower ZIKV transmission rates were observed for NHUV/ZIKV dually intrathoracically inoculated mosquitoes (41%) compared to ZIKV only inoculated mosquitoes (78%) (p < 0.0001), suggesting that NHUV can interfere with both midgut infection and salivary gland infection of ZIKV in Ae. aegypti. These results indicate NHUV could be utilized to model superinfection exclusion mechanism(s) and to study the potential for the mosquito virome to impact transmission of medically important flaviviruses.

Citing Articles

Risk assessment of an Aedes flavivirus and its effect on pathogenic flavivirus replication in mosquitoes.

Fu Y, Zhao W, Wu S, Li J, Liu Q, Jiang F Parasit Vectors. 2025; 18(1):88.

PMID: 40045350 PMC: 11881423. DOI: 10.1186/s13071-025-06711-4.

Differential effect of acute persistent insect-specific flavivirus infection on superinfection exclusion of West Nile, Zika and chikungunya viruses in RNAi-competent and -deficient mosquito cells.

Willemsen W, Helmes N, Overheul G, Henkens M, Spruijt R, van Rij R One Health. 2025; 20():100960.

PMID: 39845567 PMC: 11750571. DOI: 10.1016/j.onehlt.2024.100960.

Insect-specific RNA viruses detection in Field-Caught Aedes aegypti mosquitoes from Argentina using NGS technology.

Ripoll L, Iserte J, Cerrudo C, Presti D, Serrat J, Poma R PLoS Negl Trop Dis. 2025; 19(1):e0012792.

PMID: 39792957 PMC: 11756794. DOI: 10.1371/journal.pntd.0012792.

Eilat virus isolated from Culex univittatus mosquitoes from the Namibian Zambezi Region influences in vitro superinfection with alpha- and flaviviruses in a virus-species-dependent manner.

Guggemos H, Kopp A, Voigt K, Fendt M, Graff S, Mfune J PLoS One. 2024; 19(12):e0312182.

PMID: 39705228 PMC: 11661592. DOI: 10.1371/journal.pone.0312182.

New Iflavirus Species Characterized from Mosquitoes Captured in the Sao Paulo Zoological Facilities.

Guimaraes L, Bahia S, de Oliveira Ribeiro G, do Socorro Foro Ramos E, Villanova F, Morais V Microorganisms. 2024; 12(9).

PMID: 39338426 PMC: 11434248. DOI: 10.3390/microorganisms12091749.

References

Smith D, Adams A, Kenney J, Wang E, Weaver S . Venezuelan equine encephalitis virus in the mosquito vector Aedes taeniorhynchus: infection initiated by a small number of susceptible epithelial cells and a population bottleneck. Virology. 2007; 372(1):176-86. PMC: 2291444. DOI: 10.1016/j.virol.2007.10.011. View

Kent R, Crabtree M, Miller B . Transmission of West Nile virus by Culex quinquefasciatus say infected with Culex Flavivirus Izabal. PLoS Negl Trop Dis. 2010; 4(5):e671. PMC: 2864301. DOI: 10.1371/journal.pntd.0000671. View

Farfan-Ale J, Lorono-Pino M, Garcia-Rejon J, Soto V, Lin M, Staley M . Detection of flaviviruses and orthobunyaviruses in mosquitoes in the Yucatan Peninsula of Mexico in 2008. Vector Borne Zoonotic Dis. 2010; 10(8):777-83. PMC: 2976644. DOI: 10.1089/vbz.2009.0196. View

Bolling B, Eisen L, Moore C, Blair C . Insect-specific flaviviruses from Culex mosquitoes in Colorado, with evidence of vertical transmission. Am J Trop Med Hyg. 2011; 85(1):169-77. PMC: 3122363. DOI: 10.4269/ajtmh.2011.10-0474. View

Duggal N, Ritter J, Pestorius S, Zaki S, Davis B, Chang G . Frequent Zika Virus Sexual Transmission and Prolonged Viral RNA Shedding in an Immunodeficient Mouse Model. Cell Rep. 2017; 18(7):1751-1760. PMC: 5683178. DOI: 10.1016/j.celrep.2017.01.056. View

Blitvich B, Firth A . Insect-specific flaviviruses: a systematic review of their discovery, host range, mode of transmission, superinfection exclusion potential and genomic organization. Viruses. 2015; 7(4):1927-59. PMC: 4411683. DOI: 10.3390/v7041927. View

Weaver S, Reisen W . Present and future arboviral threats. Antiviral Res. 2009; 85(2):328-45. PMC: 2815176. DOI: 10.1016/j.antiviral.2009.10.008. View

Haddow A, Guzman H, Popov V, Wood T, Widen S, Haddow A . First isolation of Aedes flavivirus in the Western Hemisphere and evidence of vertical transmission in the mosquito Aedes (Stegomyia) albopictus (Diptera: Culicidae). Virology. 2013; 440(2):134-9. DOI: 10.1016/j.virol.2012.12.008. View

Hall-Mendelin S, McLean B, Bielefeldt-Ohmann H, Hobson-Peters J, Hall R, van den Hurk A . The insect-specific Palm Creek virus modulates West Nile virus infection in and transmission by Australian mosquitoes. Parasit Vectors. 2016; 9(1):414. PMC: 4960669. DOI: 10.1186/s13071-016-1683-2. View

10.

Ruckert C, Weger-Lucarelli J, Garcia-Luna S, Young M, Byas A, Murrieta R . Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes. Nat Commun. 2017; 8:15412. PMC: 5454532. DOI: 10.1038/ncomms15412. View

11.

Sang R, Gichogo A, Gachoya J, Dunster M, Ofula V, HUNT A . Isolation of a new flavivirus related to cell fusing agent virus (CFAV) from field-collected flood-water Aedes mosquitoes sampled from a dambo in central Kenya. Arch Virol. 2003; 148(6):1085-93. DOI: 10.1007/s00705-003-0018-8. View

12.

Bolling B, Olea-Popelka F, Eisen L, Moore C, Blair C . Transmission dynamics of an insect-specific flavivirus in a naturally infected Culex pipiens laboratory colony and effects of co-infection on vector competence for West Nile virus. Virology. 2012; 427(2):90-7. PMC: 3329802. DOI: 10.1016/j.virol.2012.02.016. View

13.

Zou G, Zhang B, Lim P, Yuan Z, Bernard K, Shi P . Exclusion of West Nile virus superinfection through RNA replication. J Virol. 2009; 83(22):11765-76. PMC: 2772679. DOI: 10.1128/JVI.01205-09. View

14.

Newman C, Krebs B, Anderson T, Hamer G, Ruiz M, Brawn J . Culex Flavivirus During West Nile Virus Epidemic and Interepidemic Years in Chicago, United States. Vector Borne Zoonotic Dis. 2017; 17(8):567-575. PMC: 5564057. DOI: 10.1089/vbz.2017.2124. View

15.

Crockett R, Burkhalter K, Mead D, Kelly R, Brown J, Varnado W . Culex flavivirus and West Nile virus in Culex quinquefasciatus populations in the southeastern United States. J Med Entomol. 2012; 49(1):165-74. DOI: 10.1603/me11080. View

16.

Lanciotti R, KERST A, Nasci R, Godsey M, Mitchell C, Savage H . Rapid detection of west nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. J Clin Microbiol. 2000; 38(11):4066-71. PMC: 87542. DOI: 10.1128/JCM.38.11.4066-4071.2000. View

17.

Vera-Maloof F, Saavedra-Rodriguez K, Elizondo-Quiroga A, Lozano-Fuentes S, Black Iv W . Coevolution of the Ile1,016 and Cys1,534 Mutations in the Voltage Gated Sodium Channel Gene of Aedes aegypti in Mexico. PLoS Negl Trop Dis. 2015; 9(12):e0004263. PMC: 4684211. DOI: 10.1371/journal.pntd.0004263. View

18.

Ellenberg P, Linero F, Scolaro L . Superinfection exclusion in BHK-21 cells persistently infected with Junín virus. J Gen Virol. 2007; 88(Pt 10):2730-2739. DOI: 10.1099/vir.0.83041-0. View

19.

Gould E, de Lamballerie X, Zanotto P, Holmes E . Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv Virus Res. 2003; 59:277-314. DOI: 10.1016/s0065-3527(03)59008-x. View

20.

Saiyasombat R, Bolling B, Brault A, Bartholomay L, Blitvich B . Evidence of efficient transovarial transmission of Culex flavivirus by Culex pipiens (Diptera: Culicidae). J Med Entomol. 2011; 48(5):1031-8. DOI: 10.1603/me11043. View