Identification of the flavivirus conserved residues in the envelope protein hinge region for the rational design of a candidate West Nile live-attenuated vaccine.

The flavivirus envelope protein is a class II fusion protein that drives flavivirus-cell membrane fusion. The membrane fusion process is triggered by the conformational change of the E protein from dimer in the virion to trimer, which involves the rearrangement of three domains, EDI, EDII, and EDIII. The movement between EDI and EDII initiates the formation of the E protein trimer.

Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in .

The emergence or re-emergence of several orthobunyaviruses (order: ; family: ), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families.

SARS-CoV-2 and Arthropods: A Review.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that led to the unprecedented COVID-19 pandemic exemplifies how a lack of understanding and preparedness for emerging viruses can result in consequences on a global scale. Statements that SARS-CoV-2 could not be transmitted by arthropod vectors were made without experimental support. Here we review laboratory-based research, field studies, and environmental studies to evaluate the potential for the virus to be transmitted either biologically or mechanically by arthropods.

Re-Examining the Importance of Pigs in the Transmission of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of pediatric encephalitis in Southeast Asia. The enzootic transmission of JEV involves two types of amplifying hosts, swine and avian species. The involvement of pigs in the transmission cycle makes JEV a unique pathogen because human Japanese encephalitis cases are frequently linked to the epizootic spillover from pigs, which can not only develop viremia to sustain transmission but also signs of neurotropic and reproductive disease.

Inactivation of SARS-CoV-2 in All Blood Components Using Amotosalen/Ultraviolet A Light and Amustaline/Glutathione Pathogen Reduction Technologies.

No cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transfusion-transmitted infections (TTI) have been reported. The detection of viral RNA in peripheral blood from infected patients and blood components from infected asymptomatic blood donors is, however, concerning. This study investigated the efficacy of the amotosalen/UVA light (A/UVA) and amustaline (S-303)/glutathione (GSH) pathogen reduction technologies (PRT) to inactivate SARS-CoV-2 in plasma and platelet concentrates (PC), or red blood cells (RBC), respectively.

Impact of yellow fever virus envelope protein on wild-type and vaccine epitopes and tissue tropism.

The envelope (E) protein of flaviviruses is functionally associated with viral tissue tropism and pathogenicity. For yellow fever virus (YFV), viscerotropic disease primarily involving the liver is pathognomonic for wild-type (WT) infection. In contrast, the live-attenuated vaccine (LAV) strain 17D does not cause viscerotropic disease and reversion to virulence is associated with neurotropic disease.

Treatment with dry hydrogen peroxide accelerates the decay of severe acute syndrome coronavirus-2 on non-porous hard surfaces.

Background: Disinfection of contaminated or potentially contaminated surfaces has become an integral part of the mitigation strategies for controlling coronavirus disease 2019. Whilst a broad range of disinfectants are effective in inactivating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), application of disinfectants has a low throughput in areas that receive treatments. Disinfection of large surface areas often involves the use of reactive microbiocidal materials, including ultraviolet germicidal irradiation, chlorine dioxide, and hydrogen peroxide vapor.

The Use of Arthropod-Borne Challenge Models in BSL-3Ag and BSL-4 Biocontainment.

The study of many arthropod-borne pathogens requires high biosafety considerations, including the use of specialized facilities and equipment for arthropod containment. Mosquito- and tick-borne viruses such as yellow fever, West Nile, and Crimean Congo hemorrhagic fever viruses require facilities that are suitable for housing vertebrates. Multidisciplinary studies that incorporate the vector, vertebrate, and pathogens are essential for a complete understanding of the interactions between these transmission cycle components, especially if they aim to evaluate and model relative susceptibilities of different arthropods and vertebrates to infection and transmission between these.

SARS-CoV-2 failure to infect or replicate in mosquitoes: an extreme challenge.

This research addresses public speculation that SARS-CoV-2 might be transmitted by mosquitoes. The World Health Organization has stated "To date there has been no information nor evidence to suggest that the new coronavirus could be transmitted by mosquitoes". Here we provide the first experimental data to investigate the capacity of SARS-CoV-2 to infect and be transmitted by mosquitoes.

The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.

Chikungunya virus (CHIKV), an emerging alphavirus, has infected millions of people. However, the factors modulating disease outcome remain poorly understood. Here, we show in germ-free mice or in oral antibiotic-treated conventionally housed mice with depleted intestinal microbiomes that greater CHIKV infection and spread occurs within 1 day of virus inoculation.

Protection of swine by potent neutralizing anti-Japanese encephalitis virus monoclonal antibodies derived from vaccination.

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus endemic in the Asia Pacific region. Despite use of several highly effective vaccines, it is estimated that up to 44,000 new cases of Japanese encephalitis (JE) occur every year including 14,000 deaths and 24,000 survivors with permanent sequelae. Humoral immunity induced by vaccination is critical for effective protection.

Infection and transmission of Cache Valley virus by Aedes albopictus and Aedes aegypti mosquitoes.

Background: Cache Valley virus (CVV; Bunyavirales, Peribunyaviridae) is a mosquito-borne arbovirus endemic in North America. Although severe diseases are mainly observed in pregnant ruminants, CVV has also been recognized as a zoonotic pathogen that can cause fatal encephalitis in humans. Human exposures to CVV and its related subtypes occur frequently under different ecological conditions in the New World; however, neurotropic disease is rarely reported.

Simultaneous Coinfection of Macaques with Zika and Dengue Viruses Does not Enhance Acute Plasma Viremia but Leads to Activation of Monocyte Subsets and Biphasic Release of Pro-inflammatory Cytokines.

The consequences of simultaneous infection with Zika (ZIKV) and Dengue (DENV) viruses are poorly understood. Here we show that rhesus macaques experimentally coinfected simultaneously with ZIKV and DENV-2 demonstrated ZIKV or DENV replication without an enhancement of either infection. Coinfection was accompanied by an increase in the proportions of CD14CD16 pro-inflammatory subsets of monocytes and release of pro-inflammatory cytokines in the plasma.

A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates.

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs).

Arbovirus-Mosquito Vector-Host Interactions and the Impact on Transmission and Disease Pathogenesis of Arboviruses.

Hundreds of viruses, designated as arboviruses, are transmitted by arthropod vectors in complex transmission cycles between the virus, vertebrate host, and the vector. With millions of human and animal infections per year, it is critical to improve our understanding of the interactions between the biological and environmental factors that play a critical role in pathogenesis, disease outcomes, and transmission of arboviruses. This review focuses on mosquito-borne arboviruses and discusses current knowledge of the factors and underlying mechanisms that influence infection and transmission of arboviruses and discusses critical factors and pathways that can potentially become targets for intervention and therapeutics.

A Recombinant Subunit Based Zika Virus Vaccine Is Efficacious in Non-human Primates.

Zika Virus (ZIKV), a virus with no severe clinical symptoms or sequelae previously associated with human infection, became a public health threat following an epidemic in French Polynesia 2013-2014 that resulted in neurological complications associated with infection. Although no treatment currently exists, several vaccines using different platforms are in clinical development. These include nucleic acid vaccines based on the prM-E protein from the virus and purified formalin-inactivated ZIKV vaccines (ZPIV) which are in Phase 1/2 clinical trials.

Development of reverse genetics systems and investigation of host response antagonism and reassortment potential for Cache Valley and Kairi viruses, two emerging orthobunyaviruses of the Americas.

Orthobunyaviruses such as Cache Valley virus (CVV) and Kairi virus (KRIV) are important animal pathogens. Periodic outbreaks of CVV have resulted in the significant loss of lambs on North American farms, whilst KRIV has mainly been detected in South and Central America with little overlap in geographical range. Vaccines or treatments for these viruses are unavailable.

Culex tarsalis is a competent vector species for Cache Valley virus.

Background: Cache Valley virus (CVV) is a mosquito-borne orthobunyavirus endemic in North America. The virus is an important agricultural pathogen leading to abortion and embryonic lethality in ruminant species, especially sheep. The importance of CVV in human public health has recently increased because of the report of severe neurotropic diseases.