Unleashing Nature's Allies: Comparing the Vertical Transmission Dynamics of Insect-Specific and Vertebrate-Infecting Flaviviruses in Mosquitoes

Abstract

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called "superinfection exclusion", whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISFs) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimise vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control.

Keywords: arbovirus; biological control; flavivirus; insect-specific virus; transovarial transmission; vertical transmission.

Figure 2

Flavivirus genome structure. Flaviviruses have a genome of approximately 11 kbp, with a single open reading frame (ORF) coding for seven non-structural proteins and three structural proteins. The polyprotein ORF is flanked on either side by 5′ and 3′ untranslated regions (UTRs) and is cleaved post-translationally by host and viral proteases. Image adapted from [55].

Figure 3

Flavivirus phylogenic tree created using maximum likelihood analysis of the complete polyprotein amino acid sequence. The tree was constructed using the methods described in [45], applying a Whelan and Goldman [56] evolutionary model optimised for Gamma likelihood with 1000 bootstrap iterations and using NKV as the outgroup. Sequences were derived from Genbank accession numbers: AB488408, Aedes flavivirus (AEFV); AY898809, Alfuy virus (ALFV); KU308380, Bamaga virus (BgV); KC496020, Barkedji virus (BJV); MG587038, Binjari virus (BinJV); KJ741267, cell fusing agent virus (CFAV); JQ308185, Chaoyang virus (CHAOV), AB262759, Culex flavivirus (CxFV); HE574574, Culex theileri flavivirus (CTFV); U88536, dengue virus serotype 1 (DENV-1); U87411, dengue virus serotype 2 (DENV-2); AY099336, dengue virus serotype 3 (DENV-3); AF326825, dengue virus serotype 4 (DENV-4); NC_016997, Donggang virus (DONV); DQ859060, Edge Hill virus (EHV); DQ235145, Gadgets Gully virus (GGYV); NC_030401, Hanko virus (HANKV); MN954647, Hidden Valley virus (HVV), KC692067, Ilomantsi virus (ILOV), AF217620, Japanese encephalitis virus (JEV), AY149905, Kamiti River virus (KRV); KY320648, Kampung Karu virus (KPKV); NC_035118, Karumba virus (KRBV); AY632541, Kokoberra virus (KOKV), KC692068, Lammi virus (LAMV); Y07863, Louping ill virus (LIV), KY290256, Long Pine Key virus (LPKV); NC_035187, Mac Peak virus (McPV); MF139576, Marisma mosquito virus (MMV); AJ242984, Modoc virus (MODV); AF161266, Murray Valley encephalitis virus (MVEV); NC_030400, Nakiwogo virus (NAKV), MF139575, Nanay virus (NANV); KJ210048, Nhumirim virus (NHUV); JQ957875, Nienokoue virus (NIEV); EU159426, Nounane virus (NOUV); AY193805, Omsk haemorrhagic fever virus (OHFV); KC505248, Palm Creek virus (PCV); KT192549, Parramatta River virus (PaRV); L06436, Powassan virus (POWV); FJ644291, Quang Binh virus (QBV); NC_003675, Rio Bravo virus (RBV); DQ235150, Saumarez Reef virus (SREV); DQ837642, Sepik virus (SEPV); KM225263, Stratford virus (STRV); DQ859064, Spondeweni virus (SPOV); DQ525916, St Louis encephalitis virus (SLEV); U27495, tick-borne encephalitis virus (TBEV); DQ859065, Uganda S virus (UGSV); JN226796, Wesselsbron virus (WSLV); KY229074, West Nile virus (WNV); MN1062241, yellow fever virus (YFV); AY632535, Zika virus (ZIKV).

Figure 1

Differences in transmission of arboviruses and insect-specific viruses. (A). Cycle of arbovirus transmission, with an uninfected mosquito feeding on an amplifying host and spreading the virus to other vertebrate hosts. Some host species may develop sufficient viraemia to infect feeding mosquitoes, referred to as amplifying hosts, while other host species do not develop viremias that are sufficient to infect mosquitoes and are referred to as “dead end hosts”. (B). Vertical transmission of insect-specific viruses within mosquito populations showing the transmission of the virus directly from infected mother to offspring, without the need for virus amplification in vertebrate hosts. Green dots represent viral infection.

Figure 4

Different mechanisms of vertical transmission in mosquitoes. (A) Transovarial transmission occurs in the ovaries during development, where the eggs become infected with the virus internally. (B) Transovum transmission occurs when the eggs are infected through an infected common oviduct, in which larvae become infected after hatching. Green dots represent viral infection.