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Молекулярные эпидемиологические исследования ветеринарных арбовирусных энцефалитидов.

Недавние исследования с использованием молекулярных генетических подходов внесли важный вклад в наше понимание эпидемиологии ветеринарных энцефалитидов. Вирусы с использованием птичьих энзоотических носителей, таких, как западный энцефалит (WEEV) и североамериканский восточный энцефалит (EEEV), эволюционируют как относительно небольшое число высокозащищенных генотипов, которые распространяются на широкие географические регионы; вирусы с использованием млекопитающих с более ограниченным разбросом эволюционируют в рамках нескольких генотипов, каждый из которых географически ограничен. Аналогичны

Совпадение в аннотации оригинала
Recent studies using molecular genetic approaches have made important contributions to our understanding of the epidemiology of veterinary a … tiple genotypes, each geographically restricted. Similar findings have been reported for Australian alphaviruses. This difference may be related to vertebrate host relationships and the relative mobility of mammals and avians. Whereas EEEV and Venezualan equine encephalitis virus (VEEV) utilize small mammalian hosts in the tropics, most WEEV genotypes probab …

Viruses recovered from mosquitoes and wildlife serum collected in the Murray Valley of South-eastern Australia, February 1974, during an epidemic of encephalitis.

Pools of mosquitoes collected in the Murray Valley in February, 1974, during an encephalitis epidemic yielded 239 isolates of 11 distinct viruses. These included 39 isolates of MVE virus, an incriminated causative agent of encephalitis in man, and 111 isolates of Kunjin virus, a probable causative agent. An additional isolate of MVE virus was recovered from the serum of a white-faced heron, Ardea novaehollandiae. The other 9 viruses comprised the Alpha-viruses Ross River and Sindbis, the Flavivirus, Edge Hill, the Bunyaviruses, Koongol and Wongal, the undefined Kowanyama virus, and 3 previousl

Inhibitor of the non-structural protein 2 protease shows promising efficacy in mouse models of chikungunya.

Chikungunya virus (CHIKV) is responsible for the most endemic alphavirus infections called Chikungunya. The endemicity of Chikungunya has increased over the past two decades, and it is a pathogen with pandemic potential. There is currently no approved direct-acting antiviral to treat the disease. As part of our antiviral drug discovery program focused on alphaviruses and the non-structural protein 2 protease, we discovered that J12 and J13 can inhibit CHIKV nsP2 protease and block the replication of CHIKV in cell cultures. Both compounds are metabolically stable to human liver microsomal and S…

Understanding host responses to equine encephalitis virus infection: implications for therapeutic development.

INTRODUCTION: Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne New World alphaviruses that cause encephalitis in equids and humans. These viruses can cause severe disease and death, as well as long-term severe neurological symptoms in survivors. Despite the pathogenesis and weaponization of these viruses, there are no approved therapeutics for treating infection. AREAS COVERED: In this review, we describe the molecular pathogenesis of these viruses, discuss host-pathogen interactions needed for viral replication, and highlight new avenues …

Neutralizing monoclonal antibodies to the E2 protein of chikungunya virus protects against disease in a mouse model.

Chikungunya virus (CHIKV) recently caused the largest epidemic ever recorded for this virus involving an estimated 1.4-6.5million cases, with imported cased reported in over 40 countries. The number of monoclonal antibodies specific for this re-emerging alphavirus is currently limited. Herein we describe the generation and characterisation of five monoclonal antibodies specific for the E2 glycoprotein of CHIKV. The antibodies detected a range of CHIKV isolates in several assays including ELISA, Western blot, immunofluorescence assay (IFA) and immunohistochemistry (IHC) without evidence of cros…

Early activation of the host complement system is required to restrict central nervous system invasion and limit neuropathology during Venezuelan equine encephalitis virus infection.

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus of the genus Alphavirus, family Togaviridae, that is responsible for sporadic outbreaks in human and equid populations in Central and South America. In order to ascertain the role that complement plays in resolving VEEV-induced disease, complement-deficient C3(-/-) mice were infected with a VEEV mutant (V3533) that caused mild, transient disease in immunocompetent mice. In the absence of a functional complement system, peripheral inoculation with V3533 induced much more severe encephalitis. This enhanced pathology was as…

The Acre Project: the epidemiology of malaria and arthropod-borne virus infections in a rural Amazonian population.

The authors describe the baseline malaria prevalence and arbovirus seroprevalence among 467 subjects in an ongoing cohort study in rural Amazonia. Most subjects (72.2%) reported one or more previous episodes of malaria, and 15.6% had been hospitalized for malaria, but only 3.6% of individuals five years or older had malaria parasites detected by microscopy (10 with Plasmodium vivax and 4 with P. falciparum). Antibodies to Alphavirus, Orthobunyavirus, and/or Flavivirus were detected by hemagglutination inhibition (HI) in 42.6% of subjects aged five years or older, with a higher seropositivity r…

Structures of immature flavivirus particles.

Structures of prM-containing dengue and yellow fever virus particles were determined to 16 and 25 A resolution, respectively, by cryoelectro … tal ends of the E glycoproteins in a manner similar to the organization of the glycoproteins in the alphavirus spikes. Each heterodimer is associated with an E and a prM transmembrane density. These transmembrane densities represent either an EE or prMprM antiparallel coiled coil by which each protein spans the membrane twice, leaving the C-terminus of each …

Мукосальный иммунитет, вызванный материнской иммунизацией с помощью вакцины от вируса энцефалита в Венесуэле.

Считается, что введение иммунной реакции на мукозы требует иммуногена непосредственно на поверхности мукозы. Однако было отмечено, что живые, смягченные мутанты альфавируса, венесуэльского энцефалита (VEE), вызывают защиту от вирулентного вызова дыхательной слизи даже после материнской вакцинации. В настоящем докладе мы предлагаем механизм, с помощью которого подкожная иммунизация с молекулярным клонированием с двойным мутантом VEE может стимулировать производство мукозалов против VEE IgA. Наши результаты показали, что иммунизирующий вирус распространился на лимфоидные ткани по всей мыши и пер

Совпадение в аннотации оригинала
Induction of a mucosal immune response is generally thought to require introduction of an immunogen directly onto the mucosal surface. It has been observed, however, that live, attenuated mutants of the alphavirus, Venezuelan equine encephalitis virus (VEE), induce protection from virulent challenge at the respiratory mucosa even after parenteral inoculation…

[A monoclonal antibody study of the receptor area of the Venezuelan encephalitis virus].

The receptor region for virus-cell interaction in Venezuelan equine encephalomyelitis (VEE) and Eastern equine encephalomyelitis (EEE) virus … s established. A hypothesis is suggested concerning the existence of similar regions for the entire alphavirus genus, and the role of this region in virus-cell interaction.

The La Crosse virus class II fusion glycoprotein ij loop contributes to infectivity and replication in vitro and in vivo.

Arthropod-borne viruses (arboviruses) are an emerging and evolving global public health threat, with limited antiviral treatments or vaccines available. La Crosse virus (LACV) from the Bunyavirales order is responsible for pediatric encephalitis cases in the United States, yet little is known about the infectivity of LACV. Given the structural similarities between class II fusion glycoproteins of LACV and chikungunya virus (CHIKV), an alphavirus from the Togaviridae family, we hypothesized that LACV would share similar entry mechanisms with CHIKV. To test this hypothesis, we performed choleste…

Антивирусный алкалоид Берберин сокращает вирус Чикунгунья, испытывая митогенный активированный протеин кинеаза.

Вирус Чикунгунья (ЧИКВ) заразил миллионы людей в тропических и субтропических районах с момента его возобновления в течение последнего десятилетия. Недавно мы определили нетоксичное растение алкалоид берберин как противовирусное вещество против CHIKV на экране с высокой пропускной способностью. Здесь мы показываем, что берберин эффективен в различных типах клеток против различных штаммов CHIKV, также при высоком множестве инфекций, укрепляя потенциал берберина как антивирусного препарата. Мы исключили любое воздействие этого соединения на проникновение вируса или на активность вирусного реплик

Совпадение в аннотации оригинала
UNLABELLED: Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the l … erberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. IMPORTANCE: Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we repo …

Investigating antibody cross-reactivity and transmission dynamics of alphaviruses and flaviviruses using a multiplex serological assay.

Accurate serological tools are essential for monitoring the transmission of arboviruses with pandemic potential, yet cross-reactivity between closely related viruses hampers diagnostics and surveillance. Here, we develop a high-throughput multiplex serological assay to quantify antibody responses to 28 antigens from nine arboviruses (dengue, Zika, yellow fever, West Nile, Usutu, Japanese encephalitis, chikungunya (CHIKV), Mayaro (MAYV), and O'nyong-nyong virus) and apply it to over 4000 samples from epidemiologically distinct sites on four continents. We implement a flexible analytical method

Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak.

Members of the genera Alphavirus (family Togaviridae) and Flavivirus (family Flaviridae) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and of equine cases with neurological disease signs. Serum samples were screened using a hemagglutination inhibition …

Antiviral activity of lapachol and synthetic hydroxynaphthoquinone derivatives against Mayaro virus.

The Mayaro virus (MAYV) is an arbovirus belonging to the Togaviridae family, genus Alphavirus. MAYV causes several sporadic outbreaks, affecting regions of the Americas. There are no specific antivirals for treating the disease. Therefore, studies are increasingly needed to discover effective antivirals against these neglected viruses. Thus, our study investigates the antiviral potential in vitro of a natural hydroxynaphthoquinone (QHM0001 - lapachol) and its synthetic derivatives (QHM0011, 0020 and 0110) against CMV-MAYV-nanoluc. We observed that the compounds QHM0001, 0011, 0020 and 0110 int…

Development of Covalent Inhibitors of Chikungunya Virus nsP2 Cysteine Protease Enabled by Direct-to-Biology Synthesis and Screening.

Chikungunya virus (CHIKV), an arthropod-borne alphavirus, has emerged as a global health threat due to its rapid transmission and the lack of effective antiviral therapies. The cysteine protease activity of the virus-encoded nonstructural protein 2 (nsP2) is critical for CHIKV replication, as it processes viral polyproteins and counteracts host antiviral defenses, establishing it as a highly attractive target for therapeutic intervention. In this study, we present a rapid drug development platform that integrates covalent docking with direct-to-biology (D2B) synthesis and screening to identify…

First Phosphonic-Type Inhibitors and Activity-Based Probes Specific to the O'nyong-nyong Virus Capsid Protease.

The O'nyong-nyong virus (ONNV) is a member of the Alphavirus genus isolated for the first time in 1959 in Gulu (Uganda). The main symptoms of O'nyong-nyong fever are nonspecific and flu like; a proper diagnosis at the early stage is challenging. Until today, the first ONNV epidemic in 1959-1962 remains one of the largest arbovirus outbreaks ever recorded (over 2 million cases). No specific therapy is available thus far. Capsid protease (CP) is a chymotrypsin-like serine protease that catalyzes the autoproteolytic maturation of the structural polyprotein and undergoes self-inactivation upon the…

Chronic Chikungunya Arthritis and Rheumatoid Arthritis: What They Have in Common.

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the family Togaviridae and genus Alphavirus that causes an acute febrile illness, chikungunya fever, which is transmitted to humans by Aedes species mosquitoes. During acute illness, patients have high fever, polyarthralgias or polyarthritis, maculopapular rash, headache, and myalgia that lasts for days to weeks. Following resolution of acute infection, a significant proportion of patients develop chronic chikungunya arthritis that can resemble rheumatoid arthritis. In this review, we first consider the historical background…

First Detection of Madariaga virus in Mosquitoes Collected in a Wild Environment of Northeastern Argentina.

Madariaga virus (MADV), previously known as South American eastern equine encephalitis virus (SA EEEV; family Togaviridae, genus Alphavirus), is a mosquito-borne virus associated mainly with equine disease. In 2010, the first human outbreak by MADV was reported in Central America, but the mosquito vectors and vertebrate hosts involved in the outbreak were not identified. In Argentina, the first epizootic of MADV was in 1930, and since then, several epizootics by MADV have been reported. However, the potential vectors and hosts involved in the transmission cycle remain unknown. In the present s…