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Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface.

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The hu…

Отличительные патологические изменения в мышечных мышах, заражённых вирусом Жизненно-поглощенной Вирусной долины.

лихорадка Рифт-Вэлли (RVF) — вирусная болезнь, распространяющаяся через комары в Африке и на Ближнем Востоке. В связи с их высокой иммуногенностью и рентабельным производством были изучены живые вакцины РВФ как для ветеринарного, так и для человеческого использования. Конструктивная вакцина MP-12 была условно утверждена для ветеринарного использования в США, и кандидаты на вакцину PVF нового поколения активно изучаются. Оценка вирулентного фенотипа семян или партий вакцин имеет решающее значение для обеспечения безопасности вакцин. Ранее для оценки штамма MP-12 использовались 19-дневные мыши C

Совпадение в аннотации оригинала
Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and …

Perspectives of Next-Generation Live-Attenuated Rift Valley Fever Vaccines for Animal and Human Use.

Live-attenuated Rift Valley fever (RVF) vaccines transiently replicate in the vaccinated host, thereby effectively initiating an innate and adaptive immune response. Rift Valley fever virus (RVFV)-specific neutralizing antibodies are considered the main correlate of protection. Vaccination with classical live-attenuated RVF vaccines during gestation in livestock has been associated with fetal malformations, stillbirths, and fetal demise. Facilitated by an increased understanding of the RVFV infection and replication cycle and availability of reverse genetics systems, novel rationally-designed …

Computational prediction of phytochemical inhibitors against the cap-binding domain of Rift Valley fever virus.

Rift Valley fever is a zoonotic disease that can spread through livestock and mosquitoes, and its symptoms include retinitis, photophobia, hemorrhagic fever and neurological effects. The World Health Organization has identified Rift Valley fever as one of the viral infections that has potential to cause a future epidemic. Hence, efforts are urgently needed toward development of therapeutics and vaccine against this infectious disease. Notably, the causative virus namely, the Rift Valley fever virus (RVFV), utilizes the cap-snatching mechanism for viral transcription, rendering its cap-binding …

Alternative Splicing of RIOK3 Engages the Noncanonical NFκB Pathway during Rift Valley Fever Virus Infection.

Although the noncanonical NFκB pathway was originally identified as a cellular pathway contributing to lymphoid organogenesis, in the past 20 years, its involvement in innate immunity has become more appreciated. In particular, the noncanonical NFκB pathway has been found to be activated and even exploited by some RNA viruses during infection. Intriguingly, activation of this pathway has been shown to have a role in disrupting transcription of type 1 interferon (IFN), suggesting a rationale for why this response could be co-opted by some viruses. Rift Valley fever virus (RVFV) is a trisegmente…

Antiviral and protective effect of small interfering RNAs against rift valley fever virus in vitro.

BACKGROUND: Rift Valley Fever Virus (RVFV) is an arbovirus, a zoonotic disease that resurfaces as a potential hazard beyond geographic boundaries. Fever that can proceed to encephalitis, retinitis, hemorrhagic fever, and death is the main manifestation observed in human infections. RVFV has no authorized medication. The RNA interference (RNAi) gene silencing pathway is extremely well conserved. By targeting specific genes, small interfering RNA (siRNA) can be used to suppress viral replication. The aim of this study was to design specific siRNAs against RVFV and evaluate their prophylactic and…

Detection of Rift Valley Fever virus inter-epidemic activity in Kilimanjaro Region, North Eastern Tanzania.

BACKGROUND: Rift Valley Fever virus (RVFV) is a zoonotic arbovirus of public health impact infecting livestock, wildlife, and humans mainly in Africa and other parts of the world. Despite its public health importance, mechanisms of RVFV maintenance during interepidemic periods (IEPS) remain unclear. OBJECTIVE: We aimed to examine comparatively exposure to RVFV between humans and goats and RVFV infection between humans, goats and mosquitoes. METHODS: A cross sectional study was performed in the Lower Moshi area of the Kilimanjaro region from March to June 2020. RVFV exposure was determined by…

Sporadic Rift Valley Fever Outbreaks in Humans and Animals in Uganda, October 2017-January 2018.

INTRODUCTION: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis. The Uganda Ministry of Health received alerts of suspected viral haemorrhagic fever in humans from Kiruhura, Buikwe, Kiboga, and Mityana districts. Laboratory results from Uganda Virus Research Institute indicated that human cases were positive for Rift Valley fever virus (RVFV) by polymerase chain reaction. We investigated to determine the scope of outbreaks, identify exposure factors, and recommend evidence-based control and prevention measures. METHODS: A suspected case was defined as a person with acute fever onset,…

Tilorone-Dihydrochloride Protects against Rift Valley Fever Virus Infection and Disease in the Mouse Model.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Ri…

Vaccination with Rift Valley fever virus live attenuated vaccine strain Smithburn caused meningoencephalitis in alpacas.

Rift Valley fever (RVF) is a zoonotic, viral, mosquito-borne disease that causes considerable morbidity and mortality in humans and livestock in Africa and the Arabian Peninsula. In June 2018, 4 alpaca inoculated subcutaneously with live attenuated RVF virus (RVFV) Smithburn strain exhibited pyrexia, aberrant vocalization, anorexia, neurologic signs, and respiratory distress. One animal died the evening of inoculation, and 2 at ~20 d post-inoculation. Concern regarding potential vaccine strain reversion to wild-type RVFV or vaccine-induced disease prompted autopsy of the latter two. Macroscopi…

Isotype-Specific Fc Effector Functions Enhance Antibody-Mediated Rift Valley Fever Virus Protection In Vivo.

Discovered in 1931, Rift Valley fever virus (RVFV) is an arbovirus that causes disease in humans and livestock. In humans, disease ranges from a self-limiting febrile illness to a more severe hepatitis or encephalitis. There are currently no licensed human therapeutics for RVFV disease. Given the recent advances in the use of monoclonal antibodies (MAbs) for treating infectious disease, a panel of anti-RVFV Gn glycoprotein MAbs was developed and characterized. RVFV MAbs spanned a range of neutralizing abilities and mapped to distinct epitopes along Gn. The contribution of Fc effector functions…

Ovine Fetal and Placental Lesions and Cellular Tropism in Natural Rift Valley Fever Virus Infections.

Infection with Rift Valley fever phlebovirus (RVFV) causes abortion storms and a wide variety of outcomes for both ewes and fetuses. Sheep fetuses and placenta specimens were examined during the 2010-2011 River Valley fever (RVF) outbreak in South Africa. A total of 72 fetuses were studied of which 58 were confirmed positive for RVF. Placenta specimens were available for 35 cases. Macroscopic lesions in fetuses were nonspecific and included marked edema and occasional hemorrhages in visceral organs. Microscopically, multifocal hepatic necrosis was present in 48 of 58 cases, and apoptotic bodie…

Mutational analysis of Rift Valley fever phlebovirus nucleocapsid protein indicates novel conserved, functional amino acids.

Rift Valley fever phlebovirus (RVFV; Phenuiviridae, Phlebovirus) is an important mosquito-borne pathogen of both humans and ruminants. The RVFV genome is composed of tripartite, single stranded, negative or ambisense RNAs. The small (S) segment encodes both the nucleocapsid protein (N) and the non-structural protein (NSs). The N protein is responsible for the formation of the viral ribonucleoprotein (RNP) complexes, which are essential in the virus life cycle and for the transcription and replication of the viral genome. There is currently limited knowledge surrounding the roles of the RVFV nu…

Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression.

The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm'-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed …

Has Rift Valley fever virus evolved with increasing severity in human populations in East Africa?

Rift Valley fever (RVF) outbreaks have occurred across eastern Africa from 1912 to 2010 approximately every 4-15 years, most of which have not been accompanied by significant epidemics in human populations. However, human epidemics during RVF outbreaks in eastern Africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. We review the history of RVF outbreaks in eastern Africa to identify the epidemiological factors that could have influenced its increasing severity in humans. Diverse ecological factors influence outbr…

Serological and genomic evidence of Rift Valley fever virus during inter-epidemic periods in Mauritania.

Rift Valley fever virus (RVFV) is an emerging pathogen of major concern throughout Africa and the Arabian Peninsula, affecting both livestock and humans. In the past recurrent epidemics were reported in Mauritania and studies focused on the analysis of samples from affected populations during acute outbreaks. To verify characteristics and presence of RVFV during non-epidemic periods we implemented a multi-stage serological and molecular analysis. Serum samples of small ruminants, cattle and camels were obtained from Mauritania during an inter-epidemic period in 2012-2013. This paper presents a…

Сопоставление репликации вируса лихорадки Рифт-Вэлли на североамериканском скотоводстве и линиях клеток дикой природы.

Вирус лихорадки Рифт-Вэлли (RVFV) вызывает вспышки заболеваний по всей Африке и Аравийскому полуострову, что приводит к высокой заболеваемости и смертности среди молодого домашнего скота, частым абортам у беременных животных и потенциально тяжелым или смертельным заболеваниям у людей. Возможность распространения ОВТС на Соединенные Штаты или другие страны во всем мире вызывает серьезную озабоченность в отношении животных и здоровья населения, животноводства и торговли. Механизм стойкости ОВТС в межэпидемические периоды может осуществляться путем трансовариальной передачи комаров и/или с помощь

Совпадение в аннотации оригинала
Rift Valley fever virus (RVFV) causes disease outbreaks across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spreading to the United States or other countries worldwide is of signific…

Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon.

Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae. RVFV encodes a major virulence factor, NSs, which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the v…

Inter-epidemic and between-season persistence of rift valley fever: vertical transmission or cryptic cycling?

Rift Valley fever (RVF) is an emerging zoonotic mosquito-borne infectious disease that has been identified as a risk for spread to other continents and can cause mass livestock mortality. In equatorial Africa, outbreaks of RVF are associated with high rainfall, when vector populations are at their highest. It is, however, unclear how RVF virus persists during the inter-epidemic periods and between seasons. Understanding inter-epidemic persistence as well as the role of vectors and hosts is paramount to creating effective management programmes for RVF control. We created a mathematical model fo…