Japanese encephalitis (JE), a mosquito‑borne, vaccine‑preventable disease, is endemic to much of Asia and parts of Oceania. Its main clinical manifestation, encephalitis, is associated with a 20-30% case-fatality rate and long-term sequelae in 30%-50% of survivors. During the past two decades, substantial progress has been made in JE prevention and control. Notably, several countries have introduced JE vaccine into their national immunization programs, leading to marked reductions in morbidity and mortality. Nonetheless, major challenges remain, particularly because the disease cannot be eradicated meaning high-quality, long-term JE vaccination programs must be maintained. In addition, JEV has emerged in an increasingly wide geographic area, including in widespread parts of Australia, and shifts in the age distribution of cases towards adults in some JE-endemic areas have occurred. In this review, we summarize current knowledge on JE, outline recent advances in prevention and control, and describe key persisting and emerging concerns. Addressing these issues and continuing efforts to strengthen JE immunization programs will be important to reducing the burden of this disease for populations in endemic areas now and in the future.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus transmitted by a wide range of mosquito vectors present across the African continent. RVFV has resulted in large-scale epidemics in East, West, southern, and northern Africa with additional epidemics affecting the Arabian Peninsula, Mayotte, and Comoros. In some areas, rather than large-scale isolated outbreaks, RVFV causes a fluctuating low-level endemic burden affecting livestock populations by resulting in pregnancy loss and significant production losses. RVFV risk extends into the human population when it is transmitted either by vector-borne transmission or direct contact with infected animals or animal products such as blood, meat, or milk. Following infection, 2%-3% of humans can develop severe disease manifestations including encephalitis/meningitis, hemorrhagic fever, and retinitis, with visual deficits commonly reported among survivors. While RVF cases in animals and humans have been spatially linked, the proportion and risk associated with spillover events is poorly classified. Given RVFV's dual threat to human and livestock health, it has been designated a priority pathogen by WHO for development of countermeasures. This review aims to summarize current knowledge of RVFV epidemiology, infection, and control as well as highlight key recent advances in the understanding of epidemiology and vaccine development. Multiple next-generation vaccine candidates have advanced to phase two clinical trials which offer hope for approved and commercially available human vaccines in the coming decades. However, despite these promising advancements, key gaps in knowledge remain, particularly regarding the total burden and geographic distributions of endemic and epidemic infections, shifting epidemiologic patterns, optimal vaccine use cases, and the effects of RVFV infection on pregnancy in humans living in hyperendemic regions. Many gaps in understanding persist, and RVFV remains a quintessential One Health pathogen requiring coordinated human, animal, and environmental investigation and collaboration to translate scientific advances into effective national public health strategies.

We report the detection of tick-borne encephalitis virus (TBEV) in Dermacentor reticulatus ticks collected in Poland during the 2022 season. Both Ixodes ricinus and D. reticulatus ticks were surveilled. There was limited TBEV detection found in one pool out of 106 pools (418 ticks) that were shotgun genome sequenced. The TBEV positive tick pool consisted of N = 3 adult D. reticulatus ticks. Additional hybrid-capture sequencing of this pool resulted in the first full-length genome sequence of TBEV from this tick species. The assembled genome was classified as the European subtype through phylogenetic analysis. The new TBEV sequence is phylogenetically placed closest to a 2019 Hungarian isolate, suggesting potential viral migration or shared ancestry across nearly 1,000 km. These findings expand the known geographic range of TBEV circulation in Poland and highlight the role of D. reticulatus as an important vector of TBEV.

Powassan virus (POWV) is a tick-borne Orthoflavivirus transmitted by Ixodes tick species. POWV causes fatal encephalitis in approximately 10-30% of neurological cases, and long-lasting neurological sequelae in approximately 50% of survivors. POWV entry into the central nervous system (CNS) is an important event in determining clinical outcome. In this study, we evaluated viral replication kinetics, neuropathology, as well as host immune response following POWV infection in C57BL/6J (WT) mice. Our data showed that infection with POWV by all inoculation routes, including the intravenous, intraperitoneal, intracranial and subcutaneous, led to severe neuroinvasive disease. We showed that POWV effectively replicates in WT mice, where replication and dissemination resulted in peripheral and neurotropic phases. Viral neuroinvasion correlated with severe neuropathological alterations as well as enhanced blood-brain barrier permeability. Next, we used transcriptomics to compare the induction of effector pathways in the brain during the acute and late stages of POWV infection in mice. At all examined time points, we found several dysregulated genes including genes associated with interferon signaling, neuroinflammation and cell death signaling. We detected significant increase in the protein levels of markers involved in neuroinflammation in POWV-infected brains. Immunofluorescence analyses further validated the transcriptomic findings and demonstrated increased activation of microglia (IBA1) and astrocytes (GFAP), infiltration of peripheral immune cells (CD45), and elevated neuronal cell death (TUNEL) in POWV-infected brains. Increased protein expression of caspase-3 and p16 further indicated activation of apoptotic and senescence-associated pathways. Interestingly, we detected viral RNA and found evidence of neuroinflammation persistence, albeit at lower levels, in mice that survived the acute POWV encephalitis phase. Overall, this study provides a comprehensive understanding of the pathogenic events that occur during the acute and late stages of POWV infection in mice.

Several arthropod vectors, including ticks, sand flies, and mosquitoes, play a prominent role in the introduction and spread of numerous viral diseases. Despite Algeria being at high risk of arbovirus emergence, data on the circulation of arboviruses remain limited, except for some reports on West Nile virus (WNV). Therefore, the aim of this study was to investigate the seroprevalence of antibodies against three arboviruses in several regions of the Algerian Sahara in order to document previous viral exposure. Serum samples collected from dromedaries between May and November 2023 were tested for IgG antibodies against the mosquito-borne viruses Rift Valley fever virus (RVFV) and West Nile virus (WNV), as well as the tick-borne Crimean-Congo haemorrhagic fever virus (CCHFV), using commercial ELISA kits. A total of 224, 79, and 73 serum samples were tested for RVFV, WNV, and CCHFV, respectively. The seroprevalence of IgG antibodies was 2.68% for RVFV, 50.63% for WNV, and 75.34% for CCHFV. Co-seropositivity was most frequently observed for WNV and CCHFV (20.55%, 15/73). Place of residence and sex were significantly associated with CCHFV seropositivity in dromedaries (p < 0.05). Overall, the findings suggest widespread circulation of the studied arboviruses in the eastern Algerian Sahara and indicate the possible presence of these pathogens in camels from previously unexplored regions of the country. The results also highlight the imminent risk facing Algeria, particularly from haemorrhagic viruses, and underscore the importance of strengthening arbovirus surveillance and expanding diagnostic panels to include additional arboviruses.

West Nile virus (WNV) is a zoonotic mosquito-borne flavivirus that causes West Nile disease, an emerging and re-emerging infection of major global importance. Horses are an important sentinel species for monitoring WNV circulation. Since viraemia in horses is brief and viral loads in the blood are low, serological assays are the primary tools used to monitor WNV exposure. This study aimed to estimate the seroprevalence of WNV antibodies in horses in Albania. Between 2017 and 2020, 509 serum samples were collected from apparently healthy, unvaccinated horses across different regions of the country. Samples were analysed using two commercial ELISA kits for the detection of total WNV-specific antibodies and WNV-specific IgM. Of the 509 samples tested, 143 (28.1%) were positive for total antibodies, while 12 (2.35%) were IgM-positive, indicating recent infection. As no horse tested positive in both assays, the combined seroprevalence was 30.5% (155/509; 95% CI: 26.6-34.6%), without double counting. A subset of 37 ELISA-positive sera was subsequently tested using the virus neutralisation test (VNT), the gold-standard confirmatory assay for WNV-specific antibodies. The VNT confirmed the presence of WNV-neutralising antibodies in 35/37 (94.6%) samples, with titres ranging from 1:10 to 1:640. These findings indicate widespread WNV circulation in Albania. Compared with previous reports based on samples collected in 2010-2011, seropositivity was higher and evidence of exposure was detected in previously unaffected areas, highlighting the need for continued integrated veterinary and public health surveillance.

La Crosse virus (LACV) is a mosquito-borne orthobunyavirus within the California serogroup that primarily causes neuroinvasive disease in pediatric populations in the upper Midwestern, mid-Atlantic, and southeastern states of USA. Despite its substantial impact on public health, no vaccine or effective antiviral treatment has been developed so far. In this study, we investigated the role of the cell-surface heparan sulfate proteoglycan (HSPG) in LACV cell attachment and assessed the in vitro antiviral potential of bovine lactoferrin (bLf), which interacts with both the cell surface molecules and HSPG. Our results demonstrated that HSPG facilitates LACV infection and that bLf inhibits this process in a dose-dependent manner. These observations suggest that the antiviral mechanism of bLf may involve competitive inhibition at HSPG receptor sites, thereby preventing viral attachment to the host cell membrane. This provides further insights into the antiviral activity of bLf against LACV.

West Nile virus disease is an acute infectious illness caused by infection with the West Nile virus, which was first isolated from the blood of a febrile patient in the West Nile region of Uganda in 1937. In recent decades, West Nile fever has continued to expand across endemic regions globally, with no specific antiviral treatment or vaccine currently available for prevention. This study examines the finite-time stability of a stochastic West Nile virus model. Initially, the boundedness, existence and uniqueness of the solution are established. Furthermore, by constructing a Lyapunov function and utilizing the Gronwall inequality, a sufficient condition for the finite-time stability of the West Nile virus model is derived. Finally, numerical simulations are conducted to verify the theoretical results, and the influence of noise intensity, mortality rates and transmission rates on the finite-time stability of the model are analyzed. The results show that the lower the noise intensity and transmission rates, the greater the mortality rates, and the better the system can achieve finite-time stability.

West Nile virus (WNV)-associated neurological diseases pose a global public health burden, yet no approved antiviral treatments are available. This is primarily due to the challenges of crossing the blood-brain barrier and the lengthy, costly process of drug development.

The globally distributed arbovirus West Nile virus (WNV) is expanding across Europe, with rising numbers of human cases and an increasingly broad geographic distribution. Transmitted primarily by Culex mosquitoes, WNV lineages 1 and 2 are pathogenic to humans, yet their differences in transmission dynamics remain unclear. As vertebrate hosts develop varying viremia, mosquitoes encounter a wide range of viral doses, which may influence transmission. Here, we investigated the dose-response differences between the lineages in Cx. pipiens biotype pipiens, Cx. torrentium, and Aedes albopictus. Mosquitoes were fed increasing titers of one strain of either WNV lineage, and infection and transmission were assessed after 14 days at 24 °C. Lineage 2 required lower infectious doses while causing higher transmission. Notably, Cx. torrentium was identified as a highly competent vector for lineage 2. These findings highlight important differences between WNV lineages, improve our understanding of dose-dependent transmission, and therefore support refined risk assessments in Europe.

Dengue virus and related flaviviruses are significant threats to global health, with no approved antiviral treatments available. Remdesivir triphosphate (RVn-TP) is a nucleotide analog that inhibits RNA-dependent RNA polymerases from many clinically important RNA viruses, including dengue virus. An orally bioavailable prodrug that efficiently delivers RVn-TP could facilitate early treatment for non-hospitalized dengue patients. To that end, we developed 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-remdesivir nucleoside (V2043, ODBG-P-RVn), a phospholipid prodrug that achieves RVn-TP delivery through improved oral bioavailability, potency, and pharmacokinetics. Here, we show that when compared to the parent compound remdesivir nucleoside (RVn), V2043 is a more potent in vitro inhibitor of multiple flaviviruses, including dengue, Zika, West Nile, and Japanese encephalitis viruses. In lethal prophylactic and therapeutic mouse models that recapitulate key aspects of severe dengue in humans, once-daily oral V2043 significantly decreased dengue serum viremia, clinical severity, weight loss, and mortality. Additionally, oral V2043 was well tolerated when administered daily for 14 days. These results demonstrate the potential therapeutic efficacy of V2043 to treat several clinically relevant flaviviruses, including dengue virus, the most prevalent and widespread arbovirus infection in the world.

West Nile virus (WNV) is a mosquito-borne arbovirus with significant ecological and public health implications. Its transmission cycle involves avian hosts and mosquito vectors. Many factors, including host diversity and mosquito population dynamics are known to shape epidemic patterns. In this study, we extend previous work by incorporating multiple host types, horizontal transmission among hosts, and mosquito feeding preference into a WNV model. Using a system of ordinary differential equations, we analyze the impact of variable host competence, host abundance, host community structure, and mosquito biting preference on epidemic metrics. We derive an expression for the basic reproduction number in multihost systems and qualify the impact of less competent hosts on its value. Numerical simulations explore the impact of structural variations in the model on epidemic metrics and assess the potential for less competent hosts and mosquito feeding preference to dilute the epidemic. Our findings elucidate the influence of host heterogeneity, horizontal transmission in hosts, and mosquito biting preference on the severity and dynamics of a WNV epidemic.