Rift Valley fever in animals and humans: Current perspectives

McMillen, Cynthia M.; Hartman, Amy L.

doi:10.1016/j.antiviral.2018.05.009

Cited by 44 publications

(37 citation statements)

References 88 publications

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“…In humans, the majority of RVFV infected individuals develop flu-like symptoms with fever, chills and malaise that usually resolve within 1-2 weeks. However, a small percentage of individuals develop encephalitis or haemorrhagic fever, the latter of which may have a fatal outcome 2,3 . About 10% of infected persons develop transient or permanent loss of vision resulting from retinal lesions, regardless of disease severity 3 .…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of four-segmented Rift Valley fever virus in young sheep, goats and cattle

et al. 2020

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Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. RVFV induces severe disease in newborns and abortion in pregnant ruminants. The viral genome consists of a small (S), medium (M) and large (L) RNA segment of negative polarity. The M segment encodes a glycoprotein precursor protein that is co-translationally cleaved into the two structural glycoproteins Gn and Gc, which are involved in receptor attachment and cell entry. We previously constructed a four-segmented RVFV (RVFV-4s) by splitting the M genome segment into two M-type segments encoding either Gn or Gc. RVFV-4s replicates efficiently in cell culture but was shown to be completely avirulent in mice, lambs and pregnant ewes. Here, we show that a RVFV-4s candidate vaccine for veterinary use (vRVFV-4s) does not disseminate in vaccinated animals, is not shed or spread to the environment and does not revert to virulence. Furthermore, a single vaccination of lambs, goat kids and calves was shown to induce protective immunity against a homologous challenge. Finally, the vaccine was shown to provide full protection against a genetically distinct RVFV strain. Altogether, we demonstrate that vRVFV-4s optimally combines efficacy with safety, holding great promise as a next-generation RVF vaccine.

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of four-segmented Rift Valley fever virus in young sheep, goats and cattle

et al. 2020

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“…Members of the arthropod-transmitted genus Phlebovirus (order Bunyavirales , family Phenuiviridae ) are globally emerging pathogens with significant public health and economic impacts ( 4 ). The long-known Rift Valley fever virus (RVFV) can cause encephalitis or hemorrhagic fever in humans and abortion storms and high death rates in ruminants ( 5 ). Human infection with the recently emerged severe fever with thrombocytopenia syndrome virus in Asia or the related Heartland virus in North America lead to multiorgan dysfunction with a high case fatality rate ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition

Wuerth

Habjan

Kainulainen

et al. 2020

mBio

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RNA-activated protein kinase (PKR) is a major innate immune factor that senses viral double-stranded RNA (dsRNA) and phosphorylates eukaryotic initiation factor (eIF) 2α. Phosphorylation of the α subunit converts the eIF2αβγ complex into a stoichiometric inhibitor of eukaryotic initiation factor eIF2B, thus halting mRNA translation. To escape this protein synthesis shutoff, viruses have evolved countermechanisms such as dsRNA sequestration, eIF-independent translation by an internal ribosome binding site, degradation of PKR, or dephosphorylation of PKR or of phospho-eIF2α. Here, we report that sandfly fever Sicilian phlebovirus (SFSV) confers such a resistance without interfering with PKR activation or eIF2α phosphorylation. Rather, SFSV expresses a nonstructural protein termed NSs that strongly binds to eIF2B. Although NSs still allows phospho-eIF2α binding to eIF2B, protein synthesis and virus replication are unhindered. Hence, SFSV encodes a unique PKR antagonist that acts by rendering eIF2B resistant to the inhibitory action of bound phospho-eIF2α. IMPORTANCE RNA-activated protein kinase (PKR) is one of the most powerful antiviral defense factors of the mammalian host. PKR acts by phosphorylating mRNA translation initiation factor eIF2α, thereby converting it from a cofactor to an inhibitor of mRNA translation that strongly binds to initiation factor eIF2B. To sustain synthesis of their proteins, viruses are known to counteract this on the level of PKR or eIF2α or by circumventing initiation factor-dependent translation altogether. Here, we report a different PKR escape strategy executed by sandfly fever Sicilian virus (SFSV), a member of the increasingly important group of phleboviruses. We found that the nonstructural protein NSs of SFSV binds to eIF2B and protects it from inactivation by PKR-generated phospho-eIF2α. Protein synthesis is hence maintained and the virus can replicate despite ongoing full-fledged PKR signaling in the infected cells. Thus, SFSV has evolved a unique strategy to escape the powerful antiviral PKR.

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“…In Kenya, the 1997Kenya, the /98 and 2006Kenya, the /2007 RVFV outbreaks led to 600 and 150 human deaths and over 27,000 and 700 estimated cases respectively, overstretching the limited public health resources and facilities in the North-Eastern regions of Kenya [5]. Other countries that have been affected include South Africa, Zimbabwe, Egypt, Mauritania, Senegal, Niger, Madagascar, Mayotte, Saudi Arabia and Yemen [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

High risk for human exposure to Rift Valley fever virus in communities living along livestock movement routes: A cross-sectional survey in Kenya

et al. 2020

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IntroductionMultiple outbreaks of Rift Valley Fever (RVF) with devastating effects have occurred in East Africa. These outbreaks cause disease in both livestock and humans and affect poor households most severely. Communities living in areas practicing nomadic livestock movement may be at higher risk of infection. This study sought to i) determine the human exposure to Rift Valley fever virus (RVFV) in populations living within nomadic animal movement routes in Kenya; and ii) identify risk factors for RVFV infection in these communities. MethodsA cross-sectional descriptive study design was used. Samples were collected from the year 2014 to 2015 in a community-based sampling exercise involving healthy individuals aged �18 years from Isiolo, Tana River, and Garissa counties. In total, 1210 samples were screened by ELISA for the presence of immunoglobulin IgM and IgG antibodies against RVFV. Positive results were confirmed by plaque reduction neutralization test. ResultsOverall, IgM and IgG prevalence for all sites combined was 1.4% (95% CI 0.8-2.3%) and 36.4% (95% CI 33.8-39.2%), respectively. Isiolo County recorded a non-significant higher IgG prevalence of 38.8% than Garissa 35.9% and Tana River 32.2% (Chi square = 2.5, df = 2, p = 0.287). Males were significantly at higher risk of infection by RVFV than females (OR = 1.67, 95% CI 1.17-2.39, p<0.005). Age was significantly associated with RVFV infection (Wald Chi = 94.2, df = 5, p<0.0001). Individuals who had regular contact with cattle (OR = 1.38, 95%CI 1.01-1.89) and donkeys (OR = 1.38, 95%CI 1.14-1.67), or contact with PLOS Neglected Tropical Diseases | https://doi.The grants were awarded to M. Evander, R. Sang and C. Ahlm. The funders had no role in the study design, data collection and animals through birthing (OR = 1.69, 95%CI 1.14-2.51) were significantly at a greater risk of RVFV infection than those who did not. ConclusionThis study demonstrated that although the Isiolo County has been classified as being at medium risk for RVF, virus infection appeared to be as prevalent in humans as in Tana River and Garissa, which have been classified as being at high risk. Populations in these counties live within nomadic livestock movement routes and therefore at risk of being exposed to the RVFV. Interventions to control RVFV infections therefore, should target communities living along livestock movement pathways. Author summaryRift Valley fever (RVF) is a neglected mosquito-borne zoonotic disease that causes major outbreaks and economic harm to human and ruminants health leading to increased poverty within affected communities. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of ruminants. The virus is transmitted through bites from mosquitoes and exposure to blood, body fluids, or tissues of infected ruminants. It was first isolated in Kenya in 1930 and several outbreaks have been recorded in many countries in sub-Saharan Africa. We studied pastoralist communities living along livestock migratory routes. Migratory livestock do move long distan...

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Rift Valley fever in animals and humans: Current perspectives

Cited by 44 publications

References 88 publications

Safety and efficacy of four-segmented Rift Valley fever virus in young sheep, goats and cattle

Safety and efficacy of four-segmented Rift Valley fever virus in young sheep, goats and cattle

eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition

High risk for human exposure to Rift Valley fever virus in communities living along livestock movement routes: A cross-sectional survey in Kenya

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