Bunyaviridae nonstructural S proteins

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Bunyaviridae nonstructural S proteins (NSs) are synthesized by viral DNA/RNA and do not play a role in the replication or the viral protein coating. [1] The nonstructural S segment (NSs) created by Bunyaviridae virus family, are able to interact with the human immune system, in order to increase their replication in infected cells. [2] Understanding this mechanism can have global health impacts. [3]

Contents

Inhibition pathways

Within the Bunyaviridae virus family, specifically phlebovirus genus, there has been multiple pathways of the inhibition of the immune response. [3] NSs proteins are able to interact with interferon (INF) pathways, but the mechanism varies from virus to virus. [4] The NSs protein in different viruses have been shown to differ in amino acid sequence by up to 85%. [5]

Rift Valley Fever Virus (RVFV)

NSs protein is distributed throughout the cytoplasm and nucleus of the RVFV-infected cell. The protein created fiber-like substances within the nucleus. [3] NSs in RVFV to the SAP30 region of DNA in the nucleus of the cell, which is an important promotor region of INF-b. [6] Many other NSs proteins in the Bunyaviridae virus family do not function in this same way. [5]

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV)

Although the exact target of the SFTSV is unknown, many believe that the virus attacks human hemopoietic cells. [7] It has been shown that upstream molecules of INFs are unchanged in infected cells, such as MAVS, TRAF6 and TRAF3. [7] This suggests that INFs are still being produced, but they have no effect and are undetectable in people's blood serum. [6] The NSs protein in SFTSV has been shown to interfere with TBK1 which is needed in the activation of both IRF and NF-κB pathways. [7]

Uukuniemi virus (UUKV)

UUKV is a non-human pathogen that still creates a NSs protein. [5] The NSs protein has only been shown to weakly interact with the 40s subunit of ribosomes and MAVS. [8] [9] [10]

Arumowot virus (AMTV)

AMTV is another non-human pathogen and its NSs protein is quickly degraded by proteasomes, and therefore doesn't cause infection in humans. [11]

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Rift Valley fever (RVF) is a viral disease of humans and livestock that can cause mild to severe symptoms. The mild symptoms may include: fever, muscle pains, and headaches which often last for up to a week. The severe symptoms may include: loss of sight beginning three weeks after the infection, infections of the brain causing severe headaches and confusion, and bleeding together with liver problems which may occur within the first few days. Those who have bleeding have a chance of death as high as 50%.

<span class="mw-page-title-main">Chikungunya</span> Infection caused by the chikungunya virus

Chikungunya is an infection caused by the Alphavirus chikungunya (CHIKV). The disease was first identified in 1952 in Tanzania and named based on the Kimakonde words for "to become contorted".

<i>Dengue virus</i> Species of virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, the mainstream scientific community's understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

<i>Bunyavirales</i> Order of RNA viruses

Bunyavirales is an order of segmented negative-strand RNA viruses with mainly tripartite genomes. Member viruses infect arthropods, plants, protozoans, and vertebrates. It is the only order in the class Ellioviricetes. The name Bunyavirales derives from Bunyamwera, where the original type species Bunyamwera orthobunyavirus was first discovered. Ellioviricetes is named in honor of late virologist Richard M. Elliott for his early work on bunyaviruses.

<span class="mw-page-title-main">Arenavirus</span> Family of RNA viruses

An arenavirus is a bi- or trisegmented ambisense RNA virus that is a member of the family Arenaviridae. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have also been discovered which infect snakes to produce inclusion body disease, mostly in boa constrictors. At least eight arenaviruses are known to cause human disease. The diseases derived from arenaviruses range in severity. Aseptic meningitis, a severe human disease that causes inflammation covering the brain and spinal cord, can arise from the lymphocytic choriomeningitis virus. Hemorrhagic fever syndromes, including Lassa fever, are derived from infections such as Guanarito virus, Junin virus, Lassa virus, Lujo virus, Machupo virus, Sabia virus, or Whitewater Arroyo virus. Because of the epidemiological association with rodents, some arenaviruses and bunyaviruses are designated as roboviruses.

<i>Pestivirus</i> Genus of viruses

Pestivirus is a genus of viruses, in the family Flaviviridae. Viruses in the genus Pestivirus infect mammals, including members of the family Bovidae and the family Suidae. There are 11 species in this genus. Diseases associated with this genus include: hemorrhagic syndromes, abortion, and fatal mucosal disease.

<i>Phlebovirus</i> Genus of viruses

Phlebovirus is one of twenty genera of the family Phenuiviridae in the order Bunyavirales. The genus contains 66 species. It derives its name from Phlebotominae, the vectors of member species Naples phlebovirus, which is said to be ultimately from the Greek phlebos, meaning "vein". The proper word for "vein" in ancient Greek is however phleps (φλέψ).

<span class="mw-page-title-main">NS1 influenza protein</span>

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<span class="mw-page-title-main">STAT2</span> Protein-coding gene in Homo sapiens

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). It functions as a transcription factor downstream of type I interferons. STAT2 sequence identity between mouse and human is only 68%.

NSP1 (NS53), the product of rotavirus gene 5, is a nonstructural RNA-binding protein that contains a cysteine-rich region and is a component of early replication intermediates. RNA-folding predictions suggest that this region of the NSP1 mRNA can interact with itself, producing a stem-loop structure similar to that found near the 5'-terminus of the NSP1 mRNA.

Bunyamwera orthobunyavirus (BUNV) is a negative-sense, single-stranded enveloped RNA virus. It is assigned to the Orthobunyavirus genus, in the Bunyavirales order.

Dabie bandavirus, also called SFTS virus, is a tick-borne virus in the genus Bandavirus in the family Phenuiviridae, order Bunyavirales. The clinical condition it caused is known as severe fever with thrombocytopenia syndrome (SFTS). SFTS is an emerging infectious disease that was first described in northeast and central China 2009 and now has also been discovered in Japan, South Korea, Vietnam and Taiwan in 2015. SFTS has a fatality rate of 12% and as high as over 30% in some areas. The major clinical symptoms of SFTS are fever, vomiting, diarrhea, multiple organ failure, thrombocytopenia, leukopenia and elevated liver enzyme levels. Another outbreak occurred in East China in the early half of 2020.

<span class="mw-page-title-main">IFNA16</span> Protein-coding gene in the species Homo sapiens

Interferon alpha-16, also known as IFN-alpha-16, is a protein that in humans is encoded by theIFNA16 gene.

<span class="mw-page-title-main">Picornain 3C</span>

Picornain 3C is a protease found in picornaviruses, which cleaves peptide bonds of non-terminal sequences. Picornain 3C’s endopeptidase activity is primarily responsible for the catalytic process of selectively cleaving Gln-Gly bonds in the polyprotein of poliovirus and with substitution of Glu for Gln, and Ser or Thr for Gly in other picornaviruses. Picornain 3C are cysteine proteases related by amino acid sequence to trypsin-like serine proteases. Picornain 3C is encoded by enteroviruses, rhinoviruses, aphtoviruses and cardioviruses. These genera of picoviruses cause a wide range of infections in humans and mammals.

Tahyna orthobunyavirus ("TAHV") is a viral pathogen of humans classified in the California encephalitis virus (CEV) serogroup of the Orthobunyavirus family in the order Bunyavirales, which is endemic to Europe, Asia, Africa and possibly China.

Batai orthobunyavirus (BATV) is a RNA virus belonging to order Bunyavirales, genus Orthobunyavirus.

Cache Valley orthobunyavirus (CVV) is a member of the order Bunyavirales, genus Orthobunyavirus, and serogroup Bunyamwera, which was first isolated in 1956 from Culiseta inornata mosquitos collected in Utah's Cache Valley. CVV is an enveloped arbovirus, nominally 80–120 nm in diameter, whose genome is composed of three single-stranded, negative-sense RNA segments. The large segment of related bunyaviruses is approximately 6800 bases in length and encodes a probable viral polymerase. The middle CVV segment has a 4463-nucleotide sequence and the smallest segment encodes for the nucleocapsid, and a second non-structural protein. CVV has been known to cause outbreaks of spontaneous abortion and congenital malformations in ruminants such as sheep and cattle. CVV rarely infects humans, but when they are infected it has caused encephalitis and multiorgan failure.

The Punta Toro virus is a member of the genus Phlebovirus of the order Bunyavirales. It was initially isolated from patients in Colombia and two key patients in Panama. Two individual serotypes of PTV were isolated from these patients, PTV-Adames (A) and PTV-Balliet (B), with PTV-A appearing to be more virulent. PTV is considered to be relatively contained to the Americas with no cases being reported outside of this region. Along with a few other human pathogenic Phleboviruses, PTV is considered to be a significant virus in terms of public health as little information is known about its clinical effects and with further research underway, PTV could have unforeseen impacts on health and virology.

Civet SARS-CoV is a coronavirus associated with severe acute respiratory syndrome coronavirus (SARS-CoV), which infected humans and caused SARS events from 2002 to 2003. It infected the masked palm civet. The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly similar, with a genome sequence similarity of about 99.8%. Because several patients infected at the early stage of the epidemic had contact with fruit-eating Japanese raccoon dog in the market, tanuki may be a direct source of human SARS coronavirus. At the end of 2003, four more people in Guangzhou, China, were infected with the disease. Sequence analysis found that the similarity with the tanuki virus reached 99.9%, and the SARS coronavirus was also caused by cases of tanuki transmission.

References

  1. ↑ Viral+Nonstructural+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  2. ↑ ZHANG, S.; ZHENG, B.; WANG, T.; LI, A.; WAN, J.; QU, J.; LI, CH.; LI, D.; LIANG, M. (2017). "NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus". Acta Virologica. 61 (3): 289–298. doi: 10.4149/av_2017_307 . ISSN   1336-2305. PMID   28854793.
  3. 1 2 3 Wu, Xiaodong; Qi, Xian; Liang, Mifang; Li, Chuan; Cardona, Carol J.; Li, Dexin; Xing, Zheng (2014). "Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus". The FASEB Journal. 28 (6): 2504–2516. doi: 10.1096/fj.13-243857 . ISSN   1530-6860. PMID   24599967. S2CID   20158858.
  4. ↑ Chaudhary, Vidyanath; Zhang, Shuo; Yuen, Kit-San; Li, Chuan; Lui, Pak-Yin; Fung, Sin-Yee; Wang, Pei-Hui; Chan, Chi-Ping; Li, Dexin; Kok, Kin-Hang; Liang, Mifang (2015). "Suppression of type I and type III IFN signalling by NSs protein of severe fever with thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation". Journal of General Virology. 96 (11): 3204–3211. doi:10.1099/jgv.0.000280. hdl: 10722/216602 . ISSN   1465-2099. PMID   26353965.
  5. 1 2 3 Leventhal, Shanna S.; Wilson, Drew; Feldmann, Heinz; Hawman, David W. (February 2021). "A Look into Bunyavirales Genomes: Functions of Non-Structural (NS) Proteins". Viruses. 13 (2): 314. doi: 10.3390/v13020314 . PMC   7922539 . PMID   33670641.
  6. 1 2 May, Nicolas Le; Mansuroglu, Zeyni; Léger, Psylvia; Josse, Thibaut; Blot, Guillaume; Billecocq, Agnès; Flick, Ramon; Jacob, Yves; Bonnefoy, Eliette; Bouloy, Michèle (2008-01-25). "A SAP30 Complex Inhibits IFN-β Expression in Rift Valley Fever Virus Infected Cells". PLOS Pathogens. 4 (1): e13. doi: 10.1371/journal.ppat.0040013 . ISSN   1553-7374. PMC   2323286 . PMID   18225953.
  7. 1 2 3 Qu, Bingqian; Qi, Xian; Wu, Xiaodong; Liang, Mifang; Li, Chuan; Cardona, Carol J.; Xu, Wayne; Tang, Fenyang; Li, Zhifeng; Wu, Bing; Powell, Kira (2012-08-15). "Suppression of the Interferon and NF-κB Responses by Severe Fever with Thrombocytopenia Syndrome Virus". Journal of Virology. 86 (16): 8388–8401. doi:10.1128/JVI.00612-12. PMC   3421730 . PMID   22623799.
  8. ↑ Rezelj, Veronica V.; Överby, Anna K.; Elliott, Richard M. (2015). "Generation of Mutant Uukuniemi Viruses Lacking the Nonstructural Protein NSs by Reverse Genetics Indicates that NSs Is a Weak Interferon Antagonist". Journal of Virology. 89 (9): 4849–4856. doi:10.1128/JVI.03511-14. PMC   4403475 . PMID   25673721.
  9. ↑ Simons, J F; Persson, R; Pettersson, R F (1992-07-01). "Association of the nonstructural protein NSs of Uukuniemi virus with the 40S ribosomal subunit". Journal of Virology. 66 (7): 4233–4241. doi:10.1128/jvi.66.7.4233-4241.1992. PMC   241227 . PMID   1534850.
  10. ↑ Rezelj, Veronica V.; Li, Ping; Chaudhary, Vidyanath; Elliott, Richard M.; Jin, Dong-Yan; Brennan, Benjamin (2017). "Differential Antagonism of Human Innate Immune Responses by Tick-Borne Phlebovirus Nonstructural Proteins". mSphere. 2 (3): e00234–17. doi:10.1128/mSphere.00234-17. PMC   5489658 . PMID   28680969.
  11. ↑ Hallam, Hoai J.; Lokugamage, Nandadeva; Ikegami, Tetsuro (2019-11-21). "Rescue of infectious Arumowot virus from cloned cDNA: Posttranslational degradation of Arumowot virus NSs protein in human cells". PLOS Neglected Tropical Diseases. 13 (11): e0007904. doi: 10.1371/journal.pntd.0007904 . ISSN   1935-2735. PMC   6894884 . PMID   31751340.
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