scholarly journals Insights into the Pathogenesis of Viral Haemorrhagic Fever Based on Virus Tropism and Tissue Lesions of Natural Rift Valley Fever

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 709
Author(s):  
Lieza Odendaal ◽  
A Sally Davis ◽  
Estelle H Venter

Rift Valley fever phlebovirus (RVFV) infects humans and a wide range of ungulates and historically has caused devastating epidemics in Africa and the Arabian Peninsula. Lesions of naturally infected cases of Rift Valley fever (RVF) have only been described in detail in sheep with a few reports concerning cattle and humans. The most frequently observed lesion in both ruminants and humans is randomly distributed necrosis, particularly in the liver. Lesions supportive of vascular endothelial injury are also present and include mild hydropericardium, hydrothorax and ascites; marked pulmonary congestion and oedema; lymph node congestion and oedema; and haemorrhages in many tissues. Although a complete understanding of RVF pathogenesis is still lacking, antigen-presenting cells in the skin are likely the early targets of the virus. Following suppression of type I IFN production and necrosis of dermal cells, RVFV spreads systemically, resulting in infection and necrosis of other cells in a variety of organs. Failure of both the innate and adaptive immune responses to control infection is exacerbated by apoptosis of lymphocytes. An excessive pro-inflammatory cytokine and chemokine response leads to microcirculatory dysfunction. Additionally, impairment of the coagulation system results in widespread haemorrhages. Fatal outcomes result from multiorgan failure, oedema in many organs (including the lungs and brain), hypotension, and circulatory shock. Here, we summarize current understanding of RVF cellular tropism as informed by lesions caused by natural infections. We specifically examine how extant knowledge informs current understanding regarding pathogenesis of the haemorrhagic fever form of RVF, identifying opportunities for future research.

Author(s):  
Johanna Lindahl ◽  
Bernard Bett ◽  
Timothy Robinson ◽  
Delia Grace

Rift Valley fever is a severe disease affecting both humans and animals. The Rift Valley fever virus can be transmitted by body fluids, and the most common way for humans to get infected is from animals. The virus is also vector-borne and can be transmitted by many species of mosquitoes. As with other vector-borne diseases, the epidemiology may vary in response to environmental changes. Here the effects of climate and land use changes on Rift Valley fever, as well as on other vector-borne diseases, are discussed. The effect of irrigation in East Africa on inter-epidemic transmission of RVF is discussed in greater detail, followed by recommendations for future research and actions.


Author(s):  
Johanna Lindahl ◽  
Bernard Bett ◽  
Timothy Robinson ◽  
Delia Grace

Rift Valley fever is a severe disease affecting both humans and animals. The Rift Valley fever virus can be transmitted by body fluids, and the most common way for humans to get infected is from animals. The virus is also vector-borne and can be transmitted by many species of mosquitoes. As with other vector-borne diseases, the epidemiology may vary in response to environmental changes. Here the effects of climate and land use changes on Rift Valley fever, as well as on other vector-borne diseases, are discussed. The effect of irrigation in East Africa on inter-epidemic transmission of RVF is discussed in greater detail, followed by recommendations for future research and actions.


2011 ◽  
Vol 19 (1) ◽  
pp. 5-10 ◽  
Author(s):  
José-Carlos Fernandez ◽  
Agnès Billecocq ◽  
Jean Paul Durand ◽  
Catherine Cêtre-Sossah ◽  
Eric Cardinale ◽  
...  

ABSTRACTRift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridaefamily,Phlebovirusgenus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines.


Author(s):  
Belén Borrego ◽  
Sandra Moreno ◽  
Nuria de la Losa ◽  
Friedemann Weber ◽  
Alejandro Brun

Rift valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes an important disease in ruminants, with great economic losses. The infection can be also transmitted to humans; therefore it is considered a major threat to both human and animal health. In a previous work, we described a novel RVFV variant selected in cell culture in the presence of the antiviral agent favipiravir that was highly attenuated in vivo. This variant displayed 24 amino acid substitutions in different viral proteins when compared to its parental viral strain, two of them located in the NSs protein that is known to be the major virulence factor of RVFV. By means of a reverse genetics system, in this work we have analyzed the effect that one of these substitutions, P82L, has in viral attenuation in vivo. Rescued viruses carrying this single amino acid change were clearly attenuated in BALB/c mice while their growth in an IFN-competent cell line as well as the production of IFN-β did not seem to be affected. However, the pattern of nuclear NSs accumulation was modified in cells infected with the mutant viruses. These results unveil a new RVFV virulence marker highlighting the multiple ways of NSs protein to modulate viral infectivity.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Moataz Alhaj

Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.


The Lancet ◽  
1985 ◽  
Vol 325 (8420) ◽  
pp. 116 ◽  
Author(s):  
J.F Saluzzo ◽  
J.P Digoutte ◽  
J.L Camicas ◽  
G Chauvancy

2020 ◽  
Vol 41 (1) ◽  
pp. 28
Author(s):  
John Bingham ◽  
Petrus Jansen van Vuren

Rift Valley fever (RVF) is a mosquito-borne viral disease, principally of ruminants, that is endemic to Africa. The causative Phlebovirus, Rift Valley fever virus (RVFV), has a broad host range and, as such, also infects humans to cause primarily a self-limiting febrile illness. A small number of human cases will also develop severe complications, including haemorrhagic fever, encephalitis and visual impairment. In parts of Africa, it is a major disease of domestic ruminants, causing epidemics of abortion and mortality. It infects and can be transmitted by a broad range of mosquitos, with those of the genus Aedes and Culex thought to be the major vectors. Therefore, the virus has the potential to become established beyond Africa, including in Australia, where competent vector hosts are endemic. Vaccines for humans have not yet been developed to the commercial stage. This review examines the threat of this virus, with particular reference to Australia, and assesses gaps in our knowledge that may benefit from research focus.


2021 ◽  
Author(s):  
Dina R. Weilhammer ◽  
Nicholas R. Hum ◽  
Feliza A. Bourguet ◽  
Aimy Sebastian ◽  
Doris Lam ◽  
...  

Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiate robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs-/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified microglia-specific defects in type I interferon and interferon responsive gene expression in Mavs-/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis.


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