Arthropod-borne viruses (arboviruses) circulate in nature between arthropod vectors and vertebrate hosts. Arboviruses often cause devastating diseases in vertebrate hosts, but they typically do not cause significant pathology in their arthropod vectors. Following oral acquisition of a viremic bloodmeal from a vertebrate host, the arbovirus disease cycle requires replication in the cellular environment of the arthropod vector. Once the vector has become systemically and persistently infected, the vector is able to transmit the virus to an uninfected vertebrate host. In order to systemically infect the vector, the virus must cope with innate immune responses and overcome several tissue barriers associated with the midgut and the salivary glands. In this review we describe, in detail, the typical arbovirus infection route in competent mosquito vectors. Based on what is known from the literature, we explain the nature of the tissue barriers that arboviruses are confronted with in a mosquito vector and how arboviruses might surmount these barriers. We also point out controversial findings to highlight particular areas that are not well understood and require further research efforts.

https://www.mdpi.com/1999-4915/7/7/2795/pdf

Tissue Barriers to Arbovirus Infection in Mosquitoes.

In mid-September 2000, Rift Valley fever (RVF) virus was diagnosed as the cause of infection in humans and livestock in Jizan Region, Saudi Arabia. This is the first time that this arbovirus has been found outside Africa and Madagascar. Collections of mosquitoes (Diptera: Culicidae) were therefore undertaken (from 25 September to 10 October) at eight sites during the epidemic to obtain mosquitoes for attempted RVF virus isolation. Among 23699 mosquito females tested, isolations of RVF virus were made from six of 15428 Culex (Culex) tritaeniorhynchus Giles and from seven of 8091 Aedes vexans arabiensis Patton. Minimum mosquito infection rates per 1000 at sites with infected mosquitoes were 0.3-13.8 Cx. tritaeniorhynchus and 1.94-9.03 Ae. v. arabiensis. Viral activity moved northwards as collecting was in progress and collectors: 'caught up' with the virus at the two most northerly sites on the last two trapping evenings. Other species occurred in small numbers and were identified but not tested. Both Cx. tritaeniorhynchus and Ae. v. arabiensis were susceptible to RVF virus and transmitted between hamsters, and an additional quantitative test with Cx. tritaeniorhynchus showed that 71-73% of mosquitoes became infected after ingesting 6.9-7.9 log10 FFU/mL of virus; transmission rates were 10% (post-infection day 14) and 26% (post-infection day 20). It was concluded that both species were vectors on grounds of abundance, distribution, preference for humans and sheep, the virus isolations and vector competence tests.

The 2000 epidemic of Rift Valley fever in Saudi Arabia: mosquito vector studies. [Erratum: Dec 2002, v. 16 (4), p. 464.]

Rift Valley fever (RVF), an emerging mosquito-borne zoonotic infectious viral disease caused by the RVF virus (RVFV) (Bunyaviridae: Phlebovirus), presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant potential for international spread and use in bioterrorism. RVFV has caused large, devastating periodic epizootics and epidemics in Africa over the past ∼60 years, with severe economic and nutritional impacts on humans from illness and livestock loss. In the past 15 years alone, RVFV caused tens of thousands of human cases, hundreds of human deaths, and more than 100,000 domestic animal deaths. Cattle, sheep, goats, and camels are particularly susceptible to RVF and serve as amplifying hosts for the virus. This review highlights recent research on RVF, focusing on vectors and their ecology, transmission dynamics, and use of environmental and climate data to predict disease outbreaks. Important directions for future research are also discussed.

https://www.annualreviews.org/doi/suppl/10.1146/annurev-ento-010715-023819/suppl_file/en61_linthicum_supmat.pdf

Rift Valley Fever: An Emerging Mosquito-Borne Disease*

Mosquitoes live under the endless threat of infections from different kinds of pathogens such as bacteria, parasites, and viruses. The mosquito defends itself by employing both physical and physiological barriers that resist the entry of the pathogen and the subsequent establishment of the pathogen within the mosquito. However, if the pathogen does gain entry into the insect, the insect mounts a vigorous innate cellular and humoral immune response against the pathogen, thereby limiting the pathogen’s propagation to nonpathogenic levels. This happens through three major mechanisms: phagocytosis, melanization, and lysis. During these processes, various signaling pathways that engage intense mosquito–pathogen interactions are activated. A critical overview of the mosquito immune system and latest information about the interaction between mosquitoes and pathogens are provided in this review. The conserved, innate immune pathways and specific anti-pathogenic strategies in mosquito midgut, hemolymph, salivary gland, and neural tissues for the control of pathogen propagation are discussed in detail.

Mosquito Innate Immunity

Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al.

http://d-scholarship.pitt.edu/22192/1/journal.pntd.0002790.pdf

Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever.

We evaluated Aedes atlanticus Dyar and Knab, Aedes infirmatus Dyar and Knab, Aedes vexans (Meigen), Anopheles crucians Wiedemann, Coquillettidia perturbans (Walker), Culex nigripalpus Theobald, Mansonia dyari Belkin, Heinemann, and Page, and Psorophora ferox (Von Humboldt) from Florida to determine which of these species should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America. Female mosquitoes that had fed on adult hamsters inoculated with RVFV were incubated for 7-21 d at 26 degrees C, then allowed to refeed on susceptible hamsters, and tested to determine infection, dissemination, and transmission rates. We also inoculated mosquitoes intrathoracically, held them for 7 d, and then allowed them to feed on a susceptible hamster to check for a salivary gland barrier. When exposed to hamsters with viremias > or = 10(7.6) plaque-forming units per milliliter of blood, at least some individuals in each of the species tested became infected; however, Cx. nigripalpus, An. crucians, and Ae. infirmatus were essentially incompetent vectors in the laboratory because of either a midgut escape or salivary gland barrier. Each of the other species should be considered as potential vectors and would need to be controlled if RVFV were introduced into an area where they were found. Additional studies need to be conducted with other geographic populations of these species and to determine how environmental factors affect transmission.

https://bioone.org/journals/Journal-of-Medical-Entomology/volume-50/issue-5/ME13049/Potential-for-Mosquitoes-Diptera--Culicidae-From-Florida-to-Transmit/10.1603/ME13049.pdf

Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

Within the contiguous USA, Florida is unique in having tropical and subtropical climates, a great abundance and diversity of mosquito vectors, and high rates of human travel. These factors contribute to the state being the national ground zero for exotic mosquito-borne diseases, as evidenced by local transmission of viruses spread by Aedes aegypti, including outbreaks of dengue in 2022 and Zika in 2016. Because of limited treatment options, integrated vector management is a key part of mitigating these arboviruses. Practical knowledge of when and where mosquito populations of interest exist is critical for surveillance and control efforts, and habitat predictions at various geographic scales typically rely on ecological niche modeling. However, most of these models, usually created in partnership with academic institutions, demand resources that otherwise may be too time-demanding or difficult for mosquito control programs to replicate and use effectively. Such resources may include intensive computational requirements, high spatiotemporal resolutions of data not regularly available, and/or expert knowledge of statistical analysis. Therefore, our study aims to partner with mosquito control agencies in generating operationally useful mosquito abundance models. Given the increasing threat of mosquito-borne disease transmission in Florida, our analytic approach targets recent Ae. aegypti abundance in the Tampa Bay area. We investigate explanatory variables that: 1) are publicly available, 2) require little to no preprocessing for use, and 3) are known factors associated with Ae. aegypti ecology. Out of our 4 final models, none required more than 5 out of the 36 predictors assessed (13.9%). Similar to previous literature, the strongest predictors were consistently 3- and 4-wk temperature and precipitation lags, followed closely by 1 of 2 environmental predictors: land use/land cover or normalized difference vegetation index. Surprisingly, 3 of our 4 final models included one or more socioeconomic or demographic predictors. In general, larger sample sizes of trap collections and/or citizen science observations should result in greater confidence in model predictions and validation. However, given disparities in trap collections across jurisdictions, individual county models rather than a multicounty conglomerate model would likely yield stronger model fits. Ultimately, we hope that the results of our assessment will enable more accurate and precise mosquito surveillance and control of Ae. aegypti in Florida and beyond.

/pdf/a-habitat-model-for-disease-vector-aedes-aegypti-in-the-1morlxke.pdf

Carl Boohene

Papers

Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

A Habitat Model for Disease Vector Aedes aegypti in the Tampa Bay Area, FloridA.