Interplay between the Virus and Host in Rift Valley Fever Pathogenesis

Terasaki, Kaori; Makino, Shinji

doi:10.1159/000373924

Cited by 28 publications

(24 citation statements)

References 52 publications

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“…We used VLPs derived from RVFV (family Bunyaviridae, genus Phlebovirus), a cytoplasmic RNA virus, as the vehicle for the synthesis of virus-like mRNAs in the cytoplasm. RVFV carries a tripartite, single-stranded, negative-sense RNA genome composed of L, M, and S RNA segments (34). We generated RVFV VLPs, carrying a single RNA segment, LNCR-rLuc RNA, encoding the rLuc reporter gene flanked by the 3= and 5= noncoding regions of RVFV L RNA, from cells expressing LNCR-rLuc RNA, L protein, N protein and the envelope Gn/Gc proteins, as described previously (Fig.…”

Section: Mers-cov Nsp1 and Sars-mentioning

confidence: 99%

Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin

Lokugamage

Narayanan

Nakagawa

et al. 2015

J Virol

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135

167

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The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome CoV (SARS-CoV) represent highly pathogenic human CoVs that share a property to inhibit host gene expression at the posttranscriptional level. Similar to the nonstructural protein 1 (nsp1) of SARS-CoV that inhibits host gene expression at the translational level, we report that MERS-CoV nsp1 also exhibits a conserved function to negatively regulate host gene expression by inhibiting host mRNA translation and inducing the degradation of host mRNAs. Furthermore, like SARS-CoV nsp1, the mRNA degradation activity of MERS-CoV nsp1, most probably triggered by its ability to induce an endonucleolytic RNA cleavage, was separable from its translation inhibitory function. Despite these functional similarities, MERS-CoV nsp1 used a strikingly different strategy that selectively targeted translationally competent host mRNAs for inhibition. While SARS-CoV nsp1 is localized exclusively in the cytoplasm and binds to the 40S ribosomal subunit to gain access to translating mRNAs, MERS-CoV nsp1 was distributed in both the nucleus and the cytoplasm and did not bind stably to the 40S subunit, suggesting a distinctly different mode of targeting translating mRNAs. Interestingly, consistent with this notion, MERS-CoV nsp1 selectively targeted mRNAs, which are transcribed in the nucleus and transported to the cytoplasm, for translation inhibition and mRNA degradation but spared exogenous mRNAs introduced directly into the cytoplasm or virus-like mRNAs that originate in the cytoplasm. Collectively, these data point toward a novel viral strategy wherein the cytoplasmic origin of MERS-CoV mRNAs facilitates their escape from the inhibitory effects of MERS-CoV nsp1. (1) and has spread to several other countries in the Middle East, North Africa, Europe, and Asia. MERS-CoV appears to have originated in bats (2), while accumulating evidence has also pointed to the dromedary camels as the potential animal reservoir (3, 4). MERS-CoV infection generally causes fever, cough, and pneumonia, leading to respiratory failure, and the reported case fatality rate is ϳ40%. Some MERS patients develop acute renal failure. MERS-CoV can be transmitted from person to person (5-7), and many cases have occurred in persons with chronic underlying medical conditions or immunosuppression (8). The mechanisms governing the virulence and pathogenesis of MERSCoV are largely unknown (9).Upon entry into host cells, CoV genome expression is initiated by the translation of two large precursor polyproteins, pp1a and pp1ab, which are processed by viral proteinases into 15 to 16 mature proteins; the alpha and beta CoVs encodes 16 mature nonstructural proteins (nsp1 to nsp16), while the gamma and delta CoVs lack nsp1, the most N-terminal cleavage product, and encode only 15 nsp's (10-12). While many of these proteins play an Citation Lokugamage KG, Narayanan K, Nakagawa K, Terasaki K, Ramirez SI, Tseng CK, Makino S. 2015. Middle East respiratory syndrome coro...

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Section: Mers-cov Nsp1 and Sars-mentioning

confidence: 99%

Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin

Lokugamage

Narayanan

Nakagawa

et al. 2015

J Virol

Self Cite

135

167

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“…Type I IFN has been shown to play a critical role in protecting the host from RVFV-induced disease in animal models [34]. Notably, both the NSs mutants, carrying either the M250K single mutation or the R16H/M250K double mutation, retained the ability to bind to SAP30, the factor that is targeted by NSs to inhibit IFN-β mRNA transcription.…”

Section: Importance Of Nss-mediated Transcription Inhibition In Rvfv mentioning

confidence: 99%

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

2016

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Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, causes periodic outbreaks in livestocks and humans in countries of the African continent and Middle East. RVFV NSs protein, a nonstructural protein, is a major virulence factor that exhibits several important biological properties. These include suppression of general transcription, inhibition of IFN-β promoter induction and degradation of double-stranded RNA-dependent protein kinase R. Although each of these biological functions of NSs are considered important for countering the antiviral response in the host, the individual contributions of these functions towards RVFV virulence remains unclear. To examine this, we generated two RVFV MP-12 strain-derived mutant viruses. Each carried mutations in NSs that specifically targeted its general transcription inhibition function without affecting its ability to degrade PKR and inhibit IFN-β promoter induction, through its interaction with Sin3-associated protein 30, a part of the repressor complex at the IFN-β promoter. Using these mutant viruses, we have dissected the transcription inhibition function of NSs and examined its importance in RVFV virulence. Both NSs mutant viruses exhibited a differentially impaired ability to inhibit host transcription when compared with MP-12. It has been reported that NSs suppresses general transcription by interfering with the formation of the transcription factor IIH complex, through the degradation of the p62 subunit and sequestration of the p44 subunit. Our study results lead us to suggest that the ability of NSs to induce p62 degradation is the major contributor to its general transcription inhibition property, whereas its interaction with p44 may not play a significant role in this function. Importantly, RVFV MP-12-NSs mutant viruses with an impaired general transcription inhibition function showed a reduced cytotoxicity in cell culture and attenuated virulence in young mice, compared with its parental virus MP-12, highlighting the contribution of NSs-mediated general transcription inhibition towards RVFV virulence.

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“…Хворий відчуває мерзлякуватість чи справжній озноб [37], біль голови та в м'язах тулуба і кінцівок, у ділянці нирок, ретроорбітальний біль [38]. Температура тіла швидко підвищується до 38,3-40,5 °С [39][40]. Згодом погіршується апетит, зникає смак, з'являються біль в епігастрії, фотофобія.…”

Section: (98)unclassified

Епідеміологічні Та Клінічні Особливості Гарячки Рифт-Валлі

Andreychyn¹,

Nychyk²,

Zavidnyuk³

et al. 2020

ІХ

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Мета роботи – узагальнити дані про етіологію, епідеміологічні особливості, клінічні прояви та підходи до лабораторної діагностики гарячки Рифт-Валлі, подати основні рекомендації ВООЗ і CDC стосовно профілактики та лікування цієї інфекції. Висновок. Наведені найновіші дані про хворобу, спричинену вірусом гарячки Рифт-Валлі (Rift Valley fever virus), особливості її розповсюдження, характерні клінічні симптоми та ускладнення свідчать про особливу небезпеку цього захворювання для людства. Через серйозні наслідки хвороби, можливість виникнення великих епідемій, поширення за межі Африки ГРВ включено до Міжнародних медико-санітарних правил (ММСП) 2005 року до групи інфекційних хвороб «які становлять особливу національну та регіональну проблему», а збудник віднесено до тих біологічних агентів, які офіційно визнано чинниками біологічної зброї. Вірус ГРВ здатний інфікувати багато видів тварин, призводити до розвитку тяжких захворювань серед великої рогатої худоби, овець, верблюдів і кіз. Резервуаром збудника можуть бути також антилопи і гризуни. Найчутливішими до збудника є вівці, більше 90 % інфікованих ягнят помирає. Показник викиднів серед інфікованих вагітних овець досягає майже 100 %. На даний час основними методами боротьби з цією інфекцією, згідно з основними рекомендаціями ВООЗ і CDC, є лише профілактичні заходи. Ліцензованих вакцин проти ГРВ, доступних для людини, немає. Ефективні методи лікування ще не розроблені.

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Interplay between the Virus and Host in Rift Valley Fever Pathogenesis

Cited by 28 publications

References 52 publications

Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin

Middle East Respiratory Syndrome Coronavirus nsp1 Inhibits Host Gene Expression by Selectively Targeting mRNAs Transcribed in the Nucleus while Sparing mRNAs of Cytoplasmic Origin

Mechanistic Insight into the Host Transcription Inhibition Function of Rift Valley Fever Virus NSs and Its Importance in Virulence

Епідеміологічні Та Клінічні Особливості Гарячки Рифт-Валлі

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