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Cache Valley virus (CVV) is a mosquitoborne virus that infects livestock and humans. We report results of surveillance for CVV in New York, USA, during 2000-2016; full-genome analysis of selected CVV isolates from sheep, horse, humans, and mosquitoes from New York and Canada; and phenotypic characterization of selected strains. We calculated infection rates by using the maximum-likelihood estimation method by year, region, month, and mosquito species. The highest maximum-likelihood estimations were for Anopheles spp. mosquitoes. Our phylogenetic analysis identified 2 lineages and found evidence of segment reassortment. Furthermore, our data suggest displacement of CVV lineage 1 by lineage 2 in New York and Canada. Finally, we showed increased vector competence of An. quadrimaculatus mosquitoes for lineage 2 strains of CVV compared with lineage 1 strains.

Cache Valley virus (CVV), a mosquitoborne virus, can cause neuroinvasive disease in humans and adverse reproductive outcomes in sheep and goats. In 2023, CVV RNA was detected in an aborted lamb from a flock in Arkansas, USA. We conducted a One Health investigation to explore the potential effects of CVV in Arkansas.

Abortion is one of the major threats to the livestock industry, and it also poses significant threats to public health since some of the abortifacient agents are considered zoonotic. Chlamydia abortus (C. abortus), Coxiella burnetii (C. burnetii), Listeria monocytogenes (L. monocytogenes), and Cache Valley virus (CVV) are recognized as important zoonotic and abortifacient agents of reproductive failure in small ruminants. This study determined the prevalence of these agents in ovine and caprine foetuses in Türkiye. A total of 1 226 foetuses were collected from the sheep (n = 1 144) and goats (n = 82) from different flocks between 2012 and 2017. Molecular detection methods were used to detect C. abortus, C. burnetii, and L. monocytogenes DNA and CVV RNA in aborted foetuses. In this study, C. abortus was the most prevalent abortifacient agent among the investigated ovine (264/1144) and caprine (12/82) foetuses, followed by C. burnetii with a frequency of 2.8% (32/1144) and 8.5% (7/82) in ovine and caprine foetuses, respectively. L. monocytogenes DNA was detected in 28 (2.4%) and 2 (2.4%) of the ovine and caprine foetuses, respectively. However, CVV RNA was not detected. Although the predominant mixed infection was C. abortus and C. burnetii, mixed infection of C. abortus and L. monocytogenes, and C. burnetii and L. monocytogenes were also found. The information presented in this study contributes to the understanding of the roles of C. abortus, C. burnetii, L. monocytogenes, and CVV in abortions in small ruminants, and could be beneficial for developing more effective control strategies.

Background Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of associated hosts and vectors. Although CVV is known to be widely distributed throughout North America, no studies have explored its geography or employed computational methods to explore the mammal and mosquito species likely participating in the CVV sylvatic cycle. Methods We used a literature review and online databases to compile locality data for CVV and its potential vectors and hosts. We linked location data points with climatic data via ecological niche modeling to estimate the geographical range of CVV and hotspots of transmission risk. We used background similarity tests to identify likely CVV mosquito vectors and mammal hosts to detect ecological signals from CVV sylvatic transmission. Results CVV distribution maps revealed a widespread potential viral occurrence throughout North America. Ecological niche models identified areas with climate, vectors, and hosts suitable to maintain CVV transmission. Our background similarity tests identified Aedes vexans , Culiseta inornata , and Culex tarsalis as the most likely vectors and Odocoileus virginianus (white-tailed deer) as the most likely host sustaining sylvatic transmission. Conclusions CVV has a continental-level, widespread transmission potential. Large areas of North America have suitable climate, vectors, and hosts for CVV emergence, establishment, and spread. We identified geographical hotspots that have no confirmed CVV reports to date and, in view of CVV misdiagnosis or underreporting, can guide future surveillance to specific localities and species. Graphical Abstract

We report surveillance results of Cache Valley virus (CVV; Peribunyaviridae, Orthobunyavirus) from 2017 to 2020 in New York State (NYS). Infection rates were calculated using the maximum likelihood estimation (MLE) method by year, region, and mosquito species. The highest infection rates were identified among Anopheles spp. mosquitoes and we detected the virus in Aedes albopictus for the first time in NYS. Based on our previous Anopheles quadrimaculatus vector competence results for nine CVV strains, we selected among them three stains for further characterization. These include two CVV reassortants (PA and 15041084) and one CVV lineage 2 strain (Hu-2011). We analyzed full genomes, compared in vitro growth kinetics and assessed vector competence of Aedes albopictus. Sequence analysis of the two reassortant strains (PA and 15041084) revealed 0.3%, 0.4%, and 0.3% divergence; and 1, 10, and 6 amino acid differences for the S, M, and L segments, respectively. We additionally found that the PA strain was attenuated in vertebrate (Vero) and mosquito (C6/36) cell culture. Furthemore, Ae. albopictus mosquitoes are competent vectors for CVV Hu-2011 (16.7-62.1% transmission rates) and CVV 15041084 (27.3-48.0% transmission rates), but not for the human reassortant (PA) isolate, which did not disseminate from the mosquito midgut. Together, our results demonstrate significant phenotypic variability among strains and highlight the capacity for Ae. albopictus to act as a vector of CVV.

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. High prevalence rates of neutralizing antibodies have been detected among residents in several Latin American cities. However, zoophilic mosquito species involved in the enzootic transmission are unlikely to be responsible for the transmission leading to human exposures to CVV. Mechanisms that lead to frequent human exposures to CVV remain largely unknown. In this study, competence of two anthropophilic mosquitoes, Aedes albopictus and Ae. aegypti , for CVV was determined using per os infection to determine if these species could play a role in the transmission of CVV in the domestic and peridomestic settings of urban and suburban areas. Results Aedes albopictus were highly susceptible to CVV whereas infection of Ae. aegypti occurred at a significantly lower frequency. Whilst the dissemination rates of CVV were comparable in the two species, the relatively long period to attain maximal infectious titer in Ae. aegypti demonstrated a significant difference in the replication kinetics of CVV in these species. Detection of viral RNA in saliva suggests that both Ae. albopictus and Ae. aegypti are competent vectors for CVV under laboratory conditions. Conclusions Differential susceptibility to CVV was observed in Ae. albopictus and Ae. aegypti , reflecting their relatively different capacities for vectoring CVV in nature. The high susceptibility of Ae. albopictus to CVV observed in this study suggests its potential role as an efficient vector for CVV. Complemented by the reports of multiple CVV isolates derived from Ae. albopictus , our finding provides the basis for how the dispersal of Ae. albopictus across the New World may have a significant impact on the transmission and ecology of CVV.

Cache Valley virus (CVV) is a prevalent emerging pathogen of significant importance to agricultural and human health in North America. Emergence in livestock can result in substantial agroeconomic losses resulting from the severe embryonic lethality associated with infection during pregnancy. Although CVV pathogenesis has been well described in ruminants, small animal models are still unavailable, which limits our ability to study its pathogenesis and perform preclinical testing of therapeutics. Herein, we explored CVV pathogenesis, tissue tropism, and disease outcomes in a variety of murine models, including immune -competent and -compromised animals. Our results show that development of CVV disease in mice is dependent on innate immune responses, and type I interferon signalling is essential for preventing infection in mice. IFN-αβR -/- mice infected with CVV present with significant disease and lethal infections, with minimal differences in age-dependent pathogenesis, suggesting this model is appropriate for pathogenesis-related, and short- and long-term therapeutic studies. We also developed a novel CVV in utero transmission model that showed high rates of transmission, spontaneous abortions, and congenital malformations during infection. CVV infection presents a wide tissue tropism, with significant amplification in liver, spleen, and placenta tissues. Immune-competent mice are generally resistant to infection, and only show disease in an age dependent manner. Given the high seropositivity rates in regions of North America, and the continuing geographic expansion of competent mosquito vectors, the risk of epidemic and epizootic emergence of CVV is high, and interventions are needed for this important pathogen.

Background Vector-borne diseases are a major public health concern and cause significant morbidity and mortality. Zika virus (ZIKV) is the etiologic agent of a massive outbreak in the Americas that originated in Brazil in 2015 and shows a strong association with congenital ZIKV syndrome in newborns. Cache Valley virus (CVV) is a bunyavirus that causes mild to severe illness in humans and ruminants. In this study, we investigated the vector competence of Virginia mosquitoes for ZIKV and CVV to explore their abilities to contribute to potential outbreaks. Methods To determine vector competence, mosquitoes were fed a blood meal comprised of defibrinated sheep blood and virus. The presence of midgut or salivary gland barriers to ZIKV infection were determined by intrathoracic inoculation vs oral infection. After 14-days post-exposure, individual mosquitoes were separated into bodies, legs and wings, and saliva expectorant. Virus presence was detected by plaque assay to determine midgut infection, dissemination, and transmission rates. Results Transmission rates for Ae. albopictus orally infected (24%) and intrathoracically inoculated (63%) with ZIKV was similar to Ae. aegypti (48% and 71%, respectively). Transmission rates of ZIKV in Ae. japonicus were low, and showed evidence of a midgut infection barrier demonstrated by low midgut infection and dissemination rates from oral infection (3%), but increased transmission rates after intrathoracic inoculation (19%). Aedes triseriatus was unable to transmit ZIKV following oral infection or intrathoracic inoculation. CVV transmission was dose-dependent where mosquitoes fed high titer (ht) virus blood meals developed higher rates of midgut infection, dissemination, and transmission compared to low titer (lt) virus blood meals. CVV was detected in the saliva of Ae. albopictus (ht: 68%, lt: 24%), Ae. triseriatus (ht: 52%, lt: 7%), Ae. japonicus (ht: 22%, lt: 0%) and Ae. aegypti (ht: 10%; lt: 7%). Culex pipiens and Cx. restuans were not competent for ZIKV or CVV. Conclusions This laboratory transmission study provided further understanding of potential ZIKV and CVV transmission cycles with Aedes mosquitoes from Virginia. The ability for these mosquitoes to transmit ZIKV and CVV make them a public health concern and suggest targeted control programs by mosquito and vector abatement districts.

Seasonal abundance of mosquitoes, their viruses, and blood–feeding habits were determined at an open-faced quarry in North Branford, CT, in 2010 and 2011. This unique habitat had not previously been sampled for mosquitoes and mosquito-borne viruses. Thirty species of mosquitoes were identified from 41,719 specimens collected. Coquillettidia perturbans, Aedes trivittatus, and Ae. vexans were the most abundant species and represented 34.5%, 17.7%, and 14.8% of the totals, respectively. Jamestown Canyon virus was isolated from 6 species of mosquitoes collected from mid-June through July: Cq. perturbans (3 pools), Ae. cantator (3), Ae. trivittatus (2), Ae. aurifer (1), Ae. excrucians (1), and Culex pipiens (1). West Nile virus was cultured from 8 pools of Cx. pipiens and from 1 pool of Culiseta melanura collected from mid-August through late September. Cache Valley virus was isolated from 4 species of mosquitoes in 3 genera from about mid-August through late September 2011: Cq. perturbans (5 pools), Ae. trivittatus (2), Anopheles punctipennis (1), and An. quadrimaculatus (1). Nine different mammalian hosts were identified as sources of blood for 13 species of mosquitoes. White-tailed deer, Odocoileus virginianus, were the most common mammalian hosts (90.8%), followed by raccoon, Procyon lotor (3.1%), coyote, Canis latrans (2.4%), and human, Homo sapiens (1.2%). Exclusive mammalian blood-feeding mosquitoes included: Ae. canadensis, Ae. cantator, Ae. excrucians, Ae. japonicus, Ae. vexans, An. punctipennis, and Cx. salinarius. Fourteen species of birds, mostly Passeriformes, were identified as sources of blood from 6 mosquito species. Five species that fed on mammals (Ae. thibaulti, Ae. trivittatus, Ae. cinereus, Cq. perturbans, and Cx. pipiens) also fed on birds.

Background The threat of zoonotic diseases is significant to global public health. Campylobacter spp., Coxiella burnetii (C. burnetii), Brucella spp., Listeria monocytogenes (L. monocytogenes), Chlamydia abortus (C. abortus), and Cache Valley virus (CVV) play a role in bovine abortion and are transmitted from animals to humans. Objective This study aimed to investigate the presence of these zoonotic abortifacient agents in bovine foetuses (n = 125), each from different herds, in a three‐year period in Türkiye. Methods The detection and differentiation of Brucella spp. was achieved using a PCR method, while a multiplex PCR assay was used to detect and differentiate Campylobacter spp. Real‐time PCR assays were used to detect C. burnetii, C. abortus, and L. monocytogenes. Furthermore, samples were tested for CVV using one‐step duplex real‐time RT‐PCR. Results Although L. monocytogenes and C. abortus and CVV were not detected, Brucella spp., Campylobacter spp., and C. burnetii were detected in 19 (15.2%), 4 (3.2%), and 2 (1.6%) of the bovine foetuses, respectively. Brucella and Campylobacter species were identified by molecular testing as B. melitensis (n = 4) and B. abortus (n = 15) and C. jejuni (n = 2) and C. foetus subsp. foetus (n = 2), respectively. Conclusions The findings of this study suggest that Brucella spp., Campylobacter spp., and C. burnetii could pose a threat to both cattle and human health in the studied regions. Further studies are required to determine the exact role of these agents in cattle reproductive losses in Türkiye, as well as the economic impact of these agents on livestock. This study aimed to investigate the presence of Campylobacter spp., Coxiella burnetii, Brucella spp., Listeria monocytogenes, Chlamydia abortus, and Cache Valley virus in bovine foetuses in Türkiye. Brucella spp., Campylobacter spp. and Coxiella burnetii were detected in 19 (15.2%), 4 (3.2%) and 2 (1.6%) of the bovine foetuses, respectively. Brucella and Campylobacter species were identified by molecular testing as B. melitensis (n = 4) and B. abortus (n = 15) and C. jejuni (n = 2) and C. foetus subsp. foetus (n = 2), respectively.