African horse sickness virus NS4 protein is an important virulence factor and interferes with JAK-STAT signaling during viral infection

Wall, Gayle V.; Wright, Isabel M.; Barnardo, Carin; Erasmus, B. J.; Staden, Vida van; Potgieter, A. C.

doi:10.1016/j.virusres.2021.198407

Cited by 8 publications

(9 citation statements)

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“…The reason for this is not clear, but a possible explanation is viral immune escape mechanisms downregulating the host's response. 23 A similar observation has been made in sheep infected with the closely related Bluetongue Virus (BTV), where the animals do not develop consistent leukopenia. 24 Monocytes are a nonspecific marker of inflammation and different subpopulations with pro-and anti-inflammatory properties exist.…”

Section: Discussionmentioning

confidence: 56%

Experimental infection with African Horse Sickness Virus in horses induces only mild temporal hematologic changes and acute phase reactant response

Schliewert

Hooijberg

Steyn

et al. 2022

ajvr

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OBJECTIVE African Horse Sickness (AHS) is a vector-borne disease endemic to sub-Saharan Africa caused by African Horse Sickness Virus (AHVS). Infections in naïve horses have high morbidity and mortality rates. AHS pathogenesis is not well understood; neither the hematologic changes nor acute phase response occurring during infection has been fully evaluated. The study’s objective was to characterize the hematologic changes and acute phase response during experimental infection with AHSV. ANIMALS 4 horses negative for AHSV group-specific antibodies. PROCEDURES In this prospective, longitudinal study conducted between November 23 and December 2, 2020, horses were experimentally infected with AHSV, and blood samples were obtained before inoculation and then every 12 hours until euthanasia. Hematologic changes and changes for serum amyloid A (SAA) and iron concentration were evaluated over time using a general linear model including natural logarithm of sampling time. RESULTS All horses were humanely euthanized due to severe clinical signs typical of AHS. Median Hct increased significantly, and the median WBC count, monocyte count, eosinophil count, and myeloperoxidase index changed significantly in all horses over time. Horses developed marked thrombocytopenia (median, 48 X 103 cells/µL; range, 21 X 103 to 58 X 103 cells/µL) while markers of platelet activation also changed significantly. Median SAA increased and serum iron concentration decreased significantly over time. CLINICAL RELEVANCE Results indicated severe thrombocytopenia with platelet activation occurs during infection with AHSV. Changes in acute phase reactants SAA and iron, while significant, were unexpectedly mild and might not be useful clinical markers.

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Section: Discussionmentioning

confidence: 56%

Experimental infection with African Horse Sickness Virus in horses induces only mild temporal hematologic changes and acute phase reactant response

Schliewert

Hooijberg

Steyn

et al. 2022

ajvr

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“…The virus is closely related to epizootic hemorrhagic disease virus (EHDV) and bluetongue virus (BTV), the type species of the genus Orbivirus [8,9]. The viral genome has 10 segments, numbered 1-10, encoding seven structural proteins (VP1-7), and five non-structural proteins (NS1-3, N3A, and NS4) [10][11][12][13]. These structural proteins are similar to those of bluetongue virus [12], and VP2, encoded by segment 2, is the most important in serotyping and eliciting a neutralizing antibody response [10,12], while VP1, VP4, and VP6 make up the viral transcription complex [10].…”

Section: African Horse Sicknessmentioning

confidence: 99%

“…Segments encoding the proteins NS1 and NS2 are highly conserved across the nine serotypes. More variable regions between the serotypes encode the proteins NS3, NS3A, NS4, as well as the outer capsid proteins [8,[10][11][12]. NS4 has recently been shown to be an important virulence factor, by disrupting JAK-STAT signaling in the innate immune and antiviral response of the host animal [11].…”

Section: African Horse Sicknessmentioning

confidence: 99%

“…More variable regions between the serotypes encode the proteins NS3, NS3A, NS4, as well as the outer capsid proteins [8,[10][11][12]. NS4 has recently been shown to be an important virulence factor, by disrupting JAK-STAT signaling in the innate immune and antiviral response of the host animal [11]. Genome reassortment and recombination is seen in AHSV and plays an important role in the evolution of orbiviruses [12,14].…”

Section: African Horse Sicknessmentioning

confidence: 99%

“…As a result, there has been recent progress on the development of recombinant and inactivated vaccines, protein, and virus-like particles [10,[38][39][40][41][42]. Reverse genetics systems and recombinant techniques are being used to develop new vaccines to target specific antigens of the AHSV, including several viral and nonstructural proteins of the virus, including the capsid proteins VP2 and VP5, as well as NS1, which may elicit an interferon gamma host antiviral response [10][11][12]16,43]. These newer technologies aim to create a DIVA vaccine, which will greatly improve the control and detection of the virus.…”

Section: African Horse Sicknessmentioning

confidence: 99%

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Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences

Clemmons

Alfson

Dutton

2021

Animals

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Animals provide food and other critical resources to most of the global population. As such, diseases of animals can cause dire consequences, especially disease with high rates of morbidity or mortality. Transboundary animal diseases (TADs) are highly contagious or transmissible, epidemic diseases, with the potential to spread rapidly across the globe and the potential to cause substantial socioeconomic and public health consequences. Transboundary animal diseases can threaten the global food supply, reduce the availability of non-food animal products, or cause the loss of human productivity or life. Further, TADs result in socioeconomic consequences from costs of control or preventative measures, and from trade restrictions. A greater understanding of the transmission, spread, and pathogenesis of these diseases is required. Further work is also needed to improve the efficacy and cost of both diagnostics and vaccines. This review aims to give a broad overview of 17 TADs, providing researchers and veterinarians with a current, succinct resource of salient details regarding these significant diseases. For each disease, we provide a synopsis of the disease and its status, species and geographic areas affected, a summary of in vitro or in vivo research models, and when available, information regarding prevention or treatment.

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