The Role of Environmental, Virological and Vector Interactions in Dictating Biological Transmission of Arthropod-Borne Viruses by Mosquitoes

Kenney, Joan L.; Brault, Aaron C.

doi:10.1016/b978-0-12-800172-1.00002-1

Cited by 44 publications

(55 citation statements)

References 250 publications

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“…The overall capacity of a mosquito to become orally infected after an infectious blood meal and to transmit the virus to the next vertebrate host is expressed as the vector competence (11). For a successful infection of the mosquito vector, arboviruses have to overcome the midgut infection and escape barriers, as well as the salivary gland barriers (12).…”

mentioning

confidence: 99%

Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes

Göertz

Fros

Miesen

et al. 2016

J Virol

114

163

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Flaviviruses, such as Zika virus, yellow fever virus, dengue virus, and West Nile virus (WNV), are a serious concern for human health. Flaviviruses produce an abundant noncoding subgenomic flavivirus RNA (sfRNA) in infected cells. sfRNA results from stalling of the host 5=-3= exoribonuclease XRN1/Pacman on conserved RNA structures in the 3= untranslated region (UTR) of the viral genomic RNA. sfRNA production is conserved in insect-specific, mosquito-borne, and tick-borne flaviviruses and flaviviruses with no known vector, suggesting a pivotal role for sfRNA in the flavivirus life cycle. Here, we investigated the function of sfRNA during WNV infection of Culex pipiens mosquitoes and evaluated its role in determining vector competence. An sfRNA1-deficient WNV was generated that displayed growth kinetics similar to those of wild-type WNV in both RNA interference (RNAi)-competent and -compromised mosquito cell lines. Small-RNA deep sequencing of WNV-infected mosquitoes indicated an active small interfering RNA (siRNA)-based antiviral response for both the wild-type and sfRNA1-deficient viruses. Additionally, we provide the first evidence that sfRNA is an RNAi substrate in vivo. Two reproducible small-RNA hot spots within the 3= UTR/sfRNA of the wild-type virus mapped to RNA stem-loops SL-III and 3= SL, which stick out of the three-dimensional (3D) sfRNA structure model. Importantly, we demonstrate that sfRNA-deficient WNV displays significantly decreased infection and transmission rates in vivo when administered via the blood meal. Finally, we show that transmission and infection rates are not affected by sfRNA after intrathoracic injection, thereby identifying sfRNA as a key driver to overcome the mosquito midgut infection barrier. This is the first report to describe a key biological function of sfRNA for flavivirus infection of the arthropod vector, providing an explanation for the strict conservation of sfRNA production. IMPORTANCEUnderstanding the flavivirus transmission cycle is important to identify novel targets to interfere with disease and to aid development of virus control strategies. Flaviviruses produce an abundant noncoding viral RNA called sfRNA in both arthropod and mammalian cells. To evaluate the role of sfRNA in flavivirus transmission, we infected mosquitoes with the flavivirus West Nile virus and an sfRNA-deficient mutant West Nile virus. We demonstrate that sfRNA determines the infection and transmission rates of West Nile virus in Culex pipiens mosquitoes. Comparison of infection via the blood meal versus intrathoracic injection, which bypasses the midgut, revealed that sfRNA is important to overcome the mosquito midgut barrier. We also show that sfRNA is processed by the antiviral RNA interference machinery in mosquitoes. This is the first report to describe a pivotal biological function of sfRNA in arthropods. The results explain why sfRNA production is evolutionarily conserved. Viruses from the genus Flavivirus (family Flaviviridae), such as the highly pathogenic dengue virus (DENV...

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mentioning

confidence: 99%

Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes

Göertz

Fros

Miesen

et al. 2016

J Virol

114

163

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show abstract

“…The positive effect of temperature on vector competence has been well established by previous American studies on WNV, and other arboviruses (reviewed in Kenney & Brault 2014). Several studies confirmed that vector competence of European mosquitoes for WNV increases with temperature (Fros et al 2015a, Fros et al 2015b, Vogels et al 2016a.…”

Section: European Vector Competence Studies On Wnvmentioning

confidence: 49%

“…The ability of a vector to acquire, maintain, and transmit a pathogen can be defined as vector competence (Kenney & Brault 2014). Vector competence was hypothesized to be an important factor which may explain the differences in WNV outbreaks between northern and southern Europe.…”

Section: Vector Competencementioning

confidence: 99%

“…Susceptibility of such key bird species to WNV needs to be determined in order to establish the role of northern European bird species in WNV transmission. Vector competence is defined as the ability of a vector to acquire, maintain, and transmit a pathogen (Kenney & Brault 2014). In addition to vector competence, abundance and host preference are two other important traits that contribute to the efficiency with which mosquito species can transmit WNV (Kilpatrick et al 2005).…”

Section: Chaptermentioning

confidence: 99%

“…For a successful infection of the mosquito vector, WNV has to overcome various barriers within the mosquito body: the peritrophic membrane, the midgut barrier, and the salivary gland barrier. The midgut and salivary gland barriers are both further divided into an infection and an escape barrier (Figure 2; Kenney & Brault 2014). These barriers can limit virus infection both mechanically and through a range of antiviral immune responses, thereby determining the vector competence of the mosquito for a certain arbovirus.…”

Section: Mosquito Barriers To Arbovirus Infection and Transmissionmentioning

confidence: 99%

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The Role of Environmental, Virological and Vector Interactions in Dictating Biological Transmission of Arthropod-Borne Viruses by Mosquitoes

Cited by 44 publications

References 250 publications

Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes

Noncoding Subgenomic Flavivirus RNA Is Processed by the Mosquito RNA Interference Machinery and Determines West Nile Virus Transmission by Culex pipiens Mosquitoes

The role of Culex pipiens mosquitoes in transmission of West Nile virus in Europe

Novel Antiviral Strategies Against Emerging Arbovirus Infections

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