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Efficient cellular release of Rift Valley fever virus requires genomic RNA.

The Rift Valley fever virus is responsible for periodic, explosive epizootics throughout sub-Saharan Africa. The development of therapeutics targeting this virus is difficult due to a limited understanding of the viral replicative cycle. Utilizing a virus-like particle system, we have established roles for each of the viral structural components in assembly, release, and virus infectivity. The envelope glycoprotein, Gn, was discovered to be necessary and sufficient for packaging of the genome, nucleocapsid protein and the RNA-dependent RNA polymerase into virus particles. Additionally, packagi…

Rift Valley fever epidemiology, surveillance, and control: what have models contributed?

BACKGROUND: Rift Valley fever (RVF) is an emerging vector-borne zoonotic disease that represents a threat to human health, animal health, and livestock production, particularly in Africa. The epidemiology of RVF is not well understood, so that forecasting RVF outbreaks and carrying out efficient and timely control measures remains a challenge. Various epidemiological modeling tools have been used to increase knowledge on RVF epidemiology and to inform disease management policies. AIM: This narrative review gives an overview of modeling tools used to date to measure or model RVF risk in animal…

Иммунитет от вируса лихорадки Рифт-Вэлли, обеспечиваемый вектором парамиксовирусной вакцины.

Вирус лихорадки Рифт-Вэлли (RVFV) вызывает периодические крупные вспышки заболеваний среди людей и скота. Хотя этот вирус в настоящее время ограничивается африканским континентом и Аравийским полуостровом, все большую озабоченность вызывают вторжения в страны с иммунологическим наивным населением. Предпочтительными мишенями при разработке субкомпонентных вакцин, которые могут использоваться для борьбы с будущими вспышками заболеваний, являются RVFV Glycoproteins Gn и Gc. Здесь мы сообщаем о производстве Gn и Gc рекомбинантным штаммом вакцины от вируса птичьего парамиховируса Ньюкасла (NDV) и п

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Rift Valley fever virus (RVFV) causes recurrent large outbreaks among humans and livestock. Although the virus is currently confined to the African continent and the Arabian Peninsula, there is a growing concern for RVFV incursions into countries with immunologically naïve populations. The RVFV structural glycoproteins Gn and Gc are preferred targets in the …

Rift Valley fever virus seroprevalence in human rural populations of Gabon.

BACKGROUND: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by a phlebovirus and transmitted by Aedes mosquitoes. Humans can also be infected through direct contact with blood (aerosols) or tissues (placenta, stillborn) of infected animals. Although severe clinical cases can be observed, infection with RVF virus (RVFV) in humans is, in most cases, asymptomatic or causes a febrile illness without serious symptoms. In small ruminants RVFV mainly causes abortion and neonatal death. The distribution of RVFV has been well documented in many African countries, particularly in the n…

Risk factors for severe Rift Valley fever infection in Kenya, 2007.

A large Rift Valley fever (RVF) outbreak occurred in Kenya from December 2006 to March 2007. We conducted a study to define risk factors associated with infection and severe disease. A total of 861 individuals from 424 households were enrolled. Two hundred and two participants (23%) had serologic evidence of acute RVF infection. Of these, 52 (26%) had severe RVF disease characterized by hemorrhagic manifestations or death. Independent risk factors for acute RVF infection were consuming or handling products from sick animals (odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.78-3.61, pop…

Mechanism of tripartite RNA genome packaging in Rift Valley fever virus.

The Bunyaviridae family includes pathogens of medical and veterinary importance. Rift Valley fever virus (RVFV), a member in the Phlebovirus genus of the family Bunyaviridae, is endemic to sub-Saharan Africa and causes a mosquito-borne disease in ruminants and humans. Viruses in the family Bunyaviridae carry a tripartite, single-stranded, negative-sense RNA genome composed of L, M, and S RNAs. Little is known about how the three genomic RNA segments are copackaged to generate infectious bunyaviruses. We explored the mechanism that governs the copackaging of the three genomic RNAs into RVFV par…

Rift valley fever virus L protein forms a biologically active oligomer.

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) causes mosquito-borne epidemic diseases in humans and livestock. The virus carries three RNA segments, L, M, and S, of negative or ambisense polarity. L protein, an RNA-dependent RNA polymerase, encoded in the L segment, and N protein, encoded in the S segment, exert viral RNA replication and transcription. Coexpression of N, hemagglutinin (HA)-tagged L, and viral minigenome resulted in minigenome replication and transcription, a finding that demonstrated HA-tagged L was biologically active. Likewise L tagged with green fl…

Factors associated with rift valley fever in south-west Saudi Arabia.

The authors undertook a study of environmental and animal risk factors associated with Rift Valley fever (RVF) in south-west Saudi Arabia. An enzyme-linked immunosorbent assay was used to detect the presence of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the RVF virus in serum samples from sentinel animals. In addition, a further 32 known IgM-positive serum samples were tested using the reverse transcription polymerase chain reaction (RT-PCR) to detect the RVF virus genome. The results were analysed using the univariate odds ratio (OR). To control for confounding, Mant…

Update: outbreak of Rift Valley Fever--Saudi Arabia, August-November 2000.

On September 10, 2000, the Ministry of Health (MOH), Kingdom of Saudi Arabia and subsequently, the MOH of Yemen began receiving reports of unexplained hemorrhagic fever in humans and associated animal deaths and abortions from the far western Saudi-Yemeni border region. These cases subsequently were confirmed as Rift Valley fever (RVF), the first such cases on the Arabian peninsula. This report updates the findings of the ongoing investigation conducted by the Saudi Arabian MOH in collaboration with CDC and the National Institute of Virology, South Africa.

Hemostatic derangement produced by Rift Valley fever virus in rhesus monkeys.

Rift Valley fever (RVF) is an important cause of disease in animals and humans in sub-Saharan Africa. In a small percentage of human cases, the disease is complicated by hemorrhage, which often is associated with a fatal outcome. Inoculation of rhesus monkeys with the Zagazig Hospital strain of RVF virus produced a clinical picture similar to illness in humans. Ten of 17 monkeys developed clinical evidence of hemostatic impairment. When coagulation tests were performed, this group of monkeys had significant abnormalities, including evidence for disseminated intravascular coagulation. These abn…

Studies on Rift Valley fever in some African murids (Rodentia: Muridae).

Brains, spleens and livers of 2214 murids, 27 shrews and 7 dormice, trapped at 7 sites in Rhodesia, were tested in 277 pools for the presence of Rift Valley Fever virus. There were no isolations of Rift Valley Fever, but 69 isolations of an unidentified virus were obtained. Sixteen out of 867 sera had low-titre haemagglutination-inhibition activity against Rift Valley Fever antigen, but only one out of 1260 sera had neutralizing antibody. The evidence suggests that murids fail to encounter infection in nature and are unlikely to play a role in circulation and dissemination of Rift Valley Fever…

[Rift valley fever and rickettsial retinitis including fluorescein angiography (author's transl)].

Three cases of Rift Valley fever retinitis and one case of Tick Bite fever retinitis are presented. The clinical features are indistinguishable, manifesting as localised areas of retinal ischaemia and soft exudate formation. Fluorescein angiography shows that there is primary involvement of the retinal circulation without involvement of the choroidal circulation. Vascular occlusion is a feature of the retinal pathology. These patients were treated with steroids and immunosuppressives as their maculae were threatened and they all regained normal to near normal vision except in one case in whom …

Rift Valley fever epidemiology: shifting the paradigm and rethinking research priorities.

Rift Valley fever (RVF), a zoonotic mosquito-borne viral disease with erratic occurrence and complex epidemiology, results in substantial costs to veterinary and public health and national economies. Since 1985, RVF virus (RVFV) epidemiology has focused on epidemics triggered by flood-induced emergence of transovarially infected mosquitoes, following an interepidemic period during which RVFV persists primarily in floodwater Aedes spp mosquito eggs, with potential for low-level interepidemic circulation. In this Personal View, we challenge this classic framework of RVFV epidemiology, presenting…

Potent neutralizing human monoclonal antibodies protect from Rift Valley fever encephalitis.

Rift Valley fever (RVF) is an emerging arboviral disease affecting both humans and livestock. In humans, RVF displays a spectrum of clinical manifestations, including encephalitis. To date, there are no FDA-approved vaccines or therapeutics for human use, although several are in preclinical development. Few small-animal models of RVF encephalitis exist, further complicating countermeasure assessment. Human mAbs RVFV-140, RVFV-268, and RVFV-379 are recombinant potently neutralizing antibodies that prevent infection by binding the RVFV surface glycoproteins. Previous studies showed that both RVF…

Rift Valley Fever Virus Encephalitis: Viral and Host Determinants of Pathogenesis.

Rift Valley fever virus (RVFV) is a mosquito-borne virus endemic to Africa and the Middle East. RVFV infection can cause encephalitis, which is associated with significant morbidity and mortality. Studies of RVFV encephalitis following percutaneous inoculation, as would occur following a mosquito bite, have historically been limited by a lack of consistent animal models. In this review, we describe new insights into the pathogenesis of RVFV and the opportunities provided by new mouse models. We underscore the need to consider viral strain and route of inoculation when interpreting data obtaine…

RT-qPCR genotyping assays for differentiating Rift Valley fever phlebovirus strains.

Rift Valley fever phlebovirus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen. Real time RT-qPCR genotyping (GT) assays were developed to differentiate between two RVFV wild-type strains (128B-15 and SA01-1322) and a vaccine strain (MP-12). The GT assay uses a one-step RT-qPCR mix, with two different RVFV strain-specific primers (either forward or reverse) with long or short G/C tags and a common primer (either forward or reverse) for each of the 3 genomic segments. The GT assay produces PCR amplicons with unique melting temperatures that are resolved in a post PCR melt curve analysis…