290:
RNA segment and NSs on the smallest RNA segment. Bunyamwera virus NSs protein is a nonessential gene that contributes to viral pathogenesis. It has been shown that in mammalian cells, NSs induces shut-off of host protein synthesis, which leads to cell death. It also counteracts the host cell antiviral response and seems to be the main virulence factor, acting at the level of transcription by inhibiting RNA polymerase II–mediated transcription. In mosquito cells neither host cell transcription nor translation are inhibited, and although so far no function for the orthobunyavirus NSs protein has been found in mosquito cells, it seems the differential behavior of NSs could be one of the factors responsible for different outcomes of infection in mammalian and mosquito cell lines.
306:
after the onset of the illness more severe symptoms appeared including confusion, tachycardia (elevated heart rate), a rash, bilateral conjunctivitis and meningismus. The next day the patient became hypotensive and delirious. Later respiratory failure, seizures and necrosis of the fingers and toes occurred. One leg was amputated because of extensive muscle and cutaneous necrosis. Seven months after the onset of the illness the patient died of pulmonary complications. The causative agent was identified as a virus in the family
Bunyaviridae by electron microscopy. This was then identified genetically as CVV. Viremia was recorded seven days after the onset of fever; this is a longer period of viremia than what is normally observed in cases of Bunyaviridae infections.
395:
Early in this window, between 28 and 36 days, the virus leads to both central nervous system and musculoskeletal defects, while after 36 days of gestation infection only leads to musculoskeletal deformities. Death of the fetus usually occurs between 27 and 35 days gestation, when the central nervous system tissues are most susceptible. After 45–50 days of gestation CVV infection is not expected to cause harmful effects. After 76 days the fetus has a functioning immune system and antibodies to the virus are produced.
46:
218:, 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
314:
developed a fever and symptoms of meningitis. The patient was discharged, but returned the next day with nausea and vomiting. She was diagnosed with aseptic meningitis. She was discharged four days later. Two months after this she reported ongoing difficulties in word finding and headaches. CVV was identified as the causative agent by PCR, sequence analysis confirmed this identification.
318:
the true incidence of CVV disease and its full clinical range are still unknown. Given the widespread distribution of CVV and other viruses in the same serogroup in the United States it is possible some unexplained cases of severe multiorgan failure, congenital anomalies and human viral encephalitis may be due to CVV or similar viruses. More research of such cases is needed.
277:, and it occurs in the cytoplasm of the cell. Transcription of the tripartite genome is terminated by a strong hairpin loop sequence at the end of each segment. Once the virus has replicated enough, it is encapsidated. Assembly and budding of the newly synthesized virions occurs at the membranes of the
272:
The attachment, entry, replication, and release of CVV specifically have not been studied. However, there is information of the replication cycle for the genus orthobunyavirus, which CVV is a part of. A heterodimer of integral transmembrane proteins Gn and Gc form spikes on the surface of the virus
464:
Currently, there is no vaccine or known treatment available for CVV. The most effective method of protecting ruminants from CVV is to minimize their exposure to mosquito-infested areas during and shortly after breeding season. Concerning the safety of humans, it is advised that necessary precautions
394:
The symptoms the fetus develops from CVV infection are largely age dependent. At less than 28 days of gestation, the embryo usually dies and is reabsorbed by the mother. Between 28 and 45 days of gestation, infection leads to malformations in the developing fetus and occasionally leads to abortions.
317:
It is likely that CVV disease is underreported. Very few human cases have been reported despite its wide geographic distribution and the large number of mosquito species that transmit it. The rarity of CVV disease diagnosis is partly due to the fact that laboratories rarely test for CVV. Therefore,
313:
The third human case of CVV was a 63-year-old woman in New York, in
September 2011. When she was admitted to the hospital her symptoms were fever, headache, neck stiffness and photophobia. A week before she had noticed a lesion on her arm, as this began to fade a rash developed and spread. She then
309:
The second human case of CVV was a 41-year-old man from
Wisconsin in October 2003. He developed an acute illness with severe nausea, vomiting, fatigue and headache. He was diagnosed with acute aseptic meningitis. After three days the patient was released from the hospital; he reported feeling fully
289:
In terms of CVV alone, very little is known about the regulation of host-processes and interactions with host cells. However, CVVs
Bunyamwera serogroup's two non-structural proteins play an important role in infection. Bunyamwera virus (BUNV) codes for two non-structural proteins: NSm on the medium
305:
The first case was a 28-year-old man from North
Carolina in 1995. It is likely he was infected with the virus via mosquitos during a deer-hunting trip. The patient's first symptoms were muscle pain, fever, chills and a headache. He began vomiting the day after the first symptoms appeared. Six days
451:
Cache Valley virus was first isolated from mosquitoes in Utah in 1956. It derives its name from Cache Valley, an agricultural valley located in northern Utah and southeast Idaho. It is endemic to North
America, specifically Canada, Mexico, and the United States. The first confirmed human case
330:
in North
America, and while isolated in 1956, was only linked to disease in Texas in 1987 during a large occurrence of aborted and malformed lambs in a sheep flock. The virus does not only infect sheep, however, as In 2002 a survey conducted in 22 states showed 28% of cattle expressed specific
298:
Prior to 1956 there were no known cases of acute infections of Cache Valley virus (CVV) in humans. However antibodies against CVV have been reported. One study found neutralizing antibody to CVV in 12% of 356 persons surveyed in
Maryland and Virginia in the 1960s. These results and other such
443:. When the virus crossed the placenta and infected the developing fetus, it showed a tropism for the immature fetal cells of the central nervous system and skeletal muscle. Hydranencephaly has also been identified in goat kids with presumptive in utero infection with Cache Valley virus.
402:
in the brain and spinal column, ranging from microscopic in size to whole sections of the brain missing. In one laboratory case, the cerebral hemispheres were nothing more than fluid-filled sacs that were easily ruptured. The most common musculoskeletal deformations include
264:, NSs. The medium segment encodes 2 type 1 integral transmembrane glycoproteins, Gn and Gc, as well as a non-structural protein Nsm. The Gc and Gn proteins start as one precursor protein and are then cleaved cotranslationally. They are modified by N-linked glycosylation.
251:
The Cache Valley virus genome is split into three parts. The three parts are called the small, medium, and large segments, based on the number of bases. The large segment encodes the L protein, which is the RNA dependent RNA polymerase. The small segment utilizes an
310:
recovered four months later, though he experienced headaches more frequently than usual. The causative agent was observed with electron microscopy as being virions morphologically similar to bunyaviruses. Nucleotide sequencing identified the virus as CVV.
419:. While most affected lambs are stillborn, those that do survive are usually so weak they die within minutes of birth. During the time that they are alive, these lamb are reported to act abnormal, such as acting weak, drowsy, or walking unsteadily.
1461:
Goldsmith CS, Ksiazek TG, Rollin PE, Comer JA, Nicholson WL, Peret TC, Erdman DD, Bellini WJ, Harcourt BH, Rota PA, Bhatnagar J, Bowen MD, Erickson BR, McMullan LK, Nichol ST, Shieh WJ, Paddock CD, Zaki SR (June 2013).
1227:"Serologic survey of cattle in the northeastern and north central United States, Virginia, Alaska, and Hawaii for antibodies to Cache Valley and antigenically related viruses (Bunyamwera serogroup virus)"
273:
particle. They are involved in virus attachment and cell fusion. Once inside the cell, the viral membrane fuses with the endosomal membrane, and the virus genome is released. Transcription involves an
302:
CVV disease is a neuroinvasive illness. Of the three confirmed human cases of CVV disease two resulted in non-fatal meningitis, only the first case caused fatal encephalitis and multiorgan failure.
331:
antibodies to CVV. Cache Valley virus has also been identified as a cause of fetal abnormalities in goats. Other serological surveys have also shown antibodies to CVV in domestic and wild
452:
happened on
November 2, 1995. In Texas in 1987, CVV was described as a possible causative agent of disease in sheep. The white-tailed deer population has been identified as a potential
1190:
Chung SI, Livingston CW, Edwards JF, Crandell RW, Shope RE, Shelton MJ, Collisson EW (February 1990). "Evidence that Cache Valley virus induces congenital malformations in sheep".
990:
Blakqori G, Delhaye S, Habjan M, Blair CD, Sánchez-Vargas I, Olson KE, Attarzadeh-Yazdi G, Fragkoudis R, Kohl A, Kalinke U, Weiss S, Michiels T, Staeheli P, Weber F (May 2007).
391:. However, if the animal is pregnant and not protected by antibodies from a previous infection, Cache Valley virus can be very lethal to a developing fetus.
1277:
Harvey J, Smith J, Jackson N, Kreuder A, Dohlman T, Smith J (2019). "Cache Valley virus as a cause of fetal abnormalities in a litter of three Boer kids".
1044:
Sexton DJ, Rollin PE, Breitschwerdt EB, Corey GR, Myers SA, Dumais MR, Bowen MD, Goldsmith CS, Zaki SR, Nichol ST, Peters CJ, Ksiazek TG (February 1997).
1430:
Redden, R., & Dyer, N. (2011, January 13). Cache Valley Virus May Have
Affected N.D. Sheep (E. Crawford, Ed.). Retrieved December 6, 2014, from
256:
with alternative initiation sites to encode two proteins. Depending on the initiation site, it can either code for the protein that makes up the
1154:
International Office of Epizootics (2012). "Bunyaviral Diseases of Animals (excluding Rift Valley fever and Crimean—Congo haemorrhagic fever)".
1625:
1584:
1431:
1384:"Ovine arthrogryposis and central nervous system malformations associated with in utero Cache Valley virus infection: spontaneous disease"
644:"Role of the cytoplasmic tail domains of Bunyamwera orthobunyavirus glycoproteins Gn and Gc in virus assembly and morphogenesis"
1562:
859:"Bunyamwera virus nonstructural protein NSs counteracts interferon regulatory factor 3-mediated induction of early cell death"
1092:
Campbell GL, Mataczynski JD, Reisdorf ES, Powell JW, Martin DA, Lambert AJ, Haupt TE, Davis JP, Lanciotti RS (May 2006).
754:"Visualizing the replication cycle of bunyamwera orthobunyavirus expressing fluorescent protein-tagged Gc glycoprotein"
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be taken, such as, putting on mosquito repellent or layers of clothing, when being exposed to mosquito-infested areas.
17:
1163:
501:
1589:
1443:
947:
Hart TJ, Kohl A, Elliott RM (August 2009). "Role of the NSs protein in the zoonotic capacity of Orthobunyaviruses".
518:
1663:
992:"La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts"
1630:
45:
274:
1432:
http://www.ag.ndsu.edu/news/newsreleases/2011/jan-10-2011/cache-valley-virus-may-have-affected-n-d-sheep
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383:
in some cases, there are no known symptoms of infection. There is a quick period of viraemia before
1658:
906:
Thomas D, Blakqori G, Wagner V, Banholzer M, Kessler N, Elliott RM, Haller O, Weber F (July 2004).
552:
Nguyen NL, Zhao G, Hull R, Shelly MA, Wong SJ, Wu G, St George K, Wang D, Menegus MA (June 2013).
1524:
261:
489:
1513:
Hannaway N. (2014). Cache Valley Virus showing up in Ohio sheep. Ohio’s Country Journal: 1.
1464:"Cell culture and electron microscopy for identifying viruses in diseases of unknown cause"
40:
1156:
Manual of diagnostic tests and vaccines for terrestrial animals: (mammals, birds and bees)
8:
532:
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serosurveys are based on nonrandom sampling and therefore often difficult to interpret.
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Schoenian, S. (n.d.). Sheep 201: Sheep diseases A–Z. Retrieved December 5, 2014, from
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lasting 1 to 3 days, they are easily able to spread the virus to vectors including
130:
1576:
908:"Inhibition of RNA polymerase II phosphorylation by a viral interferon antagonist"
1616:
1547:
1290:
1225:
Sahu SP, Pedersen DD, Ridpath HD, Ostlund EN, Schmitt BJ, Alstad DA (July 2002).
1158:. Vol. 2 (7th ed.). Office international des épizooties. pp. 2–4.
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278:
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142:
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Encyclopedia of Arthropod-transmitted Infections of Man and Domesticated Animals
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808:"Role of Bunyamwera Orthobunyavirus NSs protein in infection of mosquito cells"
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closely related to Cache Valley virus, the virus was shown to replicate in the
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Kohl A, Clayton RF, Weber F, Bridgen A, Randall RE, Elliott RM (July 2003).
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While the virus is able to replicate in adult animals, besides a slight
693:"Functional analysis of the Bunyamwera orthobunyavirus Gc glycoprotein"
368:
348:
230:. CVV rarely infects humans, but when they are infected it has caused
412:
356:
332:
219:
215:
201:
70:
1518:
1325:"Infections by viruses of the families Bunyaviridae and Filoviridae"
1610:
1541:
1444:"Mosquito-spread virus affecting lamb crop | Pipestone County Star"
554:"Cache valley virus in a patient diagnosed with aseptic meningitis"
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416:
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and greatly reduced muscle mass, with the most severe cases having
364:
344:
1382:
Edwards JF, Livingston CW, Chung SI, Collisson EC (January 1989).
1153:
1091:
691:
Shi X, Goli J, Clark G, Brauburger K, Elliott RM (October 2009).
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371:. Therefore, deer tend to act as amplifying hosts to the virus.
1381:
336:
227:
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1043:
905:
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Shi X, van Mierlo JT, French A, Elliott RM (September 2010).
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340:
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805:
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Orthobunyavirus (n.d.). In Viral Zone. Retrieved from
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533:
http://medical-dictionary.thefreedictionary.com/Cache
387:
and the infection is cleared quickly by the animal's
551:
741:
http://viralzone.expasy.org/all_by_species/250.html
642:Shi X, Kohl A, Li P, Elliott RM (September 2007).
519:"Can Cache Valley virus trash your manufacturing?"
204:Bunyamwera, which was first isolated in 1956 from
1094:"Second human case of Cache Valley virus disease"
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641:
1046:"Life-threatening Cache Valley virus infection"
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603:"Bunyaviridae: recent biochemical developments"
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1368:http://www.sheep101.info/201/diseasesa-z.html
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806:Szemiel AM, Failloux AB, Elliott RM (2012).
427:When ewes were experimentally infected with
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398:Autopsies of infected fetuses show severe
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601:Obijeski JF, Murphy FA (October 1977).
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343:have a very high seroprevalence. With
326:Cache Valley virus is the most common
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431:, a teratogenic virus of the genus
24:
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474:
25:
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1323:Zeller H, Bouloy M (April 2000).
961:10.1111/j.1863-2378.2008.01166.x
875:10.1128/jvi.77.14.7999-8008.2003
321:
44:
293:
210:mosquitos collected in Utah's
13:
1:
517:Sims, R. (30 December 2009).
468:
459:
1563:Cache Valley orthobunyavirus
1533:Cache Valley orthobunyavirus
1291:10.1136/vetreccr-2018-000725
1204:10.1016/0378-1135(90)90001-c
825:10.1371/journal.pntd.0001823
531:Cache Valley virus. (2012).
422:
275:RNA dependent RNA polymerase
184:Cache Valley orthobunyavirus
157:Cache Valley orthobunyavirus
34:Cache Valley orthobunyavirus
7:
1063:10.1056/NEJM199702203360804
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10:
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1401:10.1177/030098588902600106
492:. In Ashford, R.W. (ed.).
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188:is a member of the order
171:
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39:
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620:10.1099/0022-1317-37-1-1
496:. CABI. pp. 101–4.
1664:Sheep and goat diseases
1480:10.3201/eid1906.130173
1342:10.20506/rst.19.1.1208
1110:10.3201/eid1205.051625
949:Zoonoses Public Health
925:10.1074/jbc.M400938200
709:10.1099/vir.0.013540-0
262:non-structural protein
214:. CVV is an enveloped
1448:Pipestone County Star
488:Grimstad, P. (2001).
339:. Of wild ruminants,
1008:10.1128/JVI.01933-06
770:10.1128/JVI.00902-10
660:10.1128/JVI.00573-07
570:10.1128/JCM.00252-13
490:"Cache Valley virus"
41:Virus classification
1450:. 16 February 2011.
437:trophoblastic cells
1602:Cache Valley virus
812:PLOS Negl Trop Dis
254:open reading frame
236:multiorgan failure
174:Cache Valley virus
18:Cache Valley virus
1654:Orthobunyaviruses
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1640:
1525:Taxon identifiers
1231:Am J Trop Med Hyg
869:(14): 7999–8008.
703:(10): 2483–2492.
454:natural reservoir
375:Symptoms in sheep
349:Culicoides midges
285:Host interactions
268:Replication cycle
207:Culiseta inornata
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1474:(6): 886–91.
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564:(6): 1966–9.
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535:Valley virus.
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1335:(1): 79–91.
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1155:
1104:(5): 854–6.
1101:
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1056:(8): 547–9.
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258:nucleocapsid
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232:encephalitis
212:Cache Valley
205:
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191:Bunyavirales
189:
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120:Bunyavirales
119:
107:
95:
83:
71:
64:
54:(unranked):
33:
1557:Wikispecies
1394:(1): 33–9.
912:J Biol Chem
697:J Gen Virol
613:(1): 1–14.
607:J Gen Virol
409:torticollis
294:Human cases
1648:Categories
1388:Vet Pathol
469:References
460:Prevention
369:mosquitoes
260:, N, or a
1617:Q19903694
1548:Q70626199
1174:914567638
423:Pathology
413:scoliosis
357:Anopheles
333:ruminants
220:ruminants
216:arbovirus
202:serogroup
151:Species:
79:Kingdom:
72:Riboviria
1611:Wikidata
1542:Wikidata
1498:23731788
1418:20357128
1351:11189728
1299:92700815
1261:39239621
1253:12363055
1128:16704854
1026:17344298
977:25312245
969:18771514
934:15150262
893:12829839
844:23029584
788:20573824
727:19570952
678:17609275
588:23515536
441:placenta
417:kyphosis
365:Culiseta
345:viraemia
242:Virology
222:such as
194:, genus
166:Synonyms
127:Family:
91:Phylum:
1590:2560364
1489:3713842
1410:2492399
1212:2107620
1119:3374447
1072:9023091
1017:1900204
996:J Virol
863:J Virol
835:3459826
779:2919021
758:J Virol
718:2885756
669:2045389
648:J Virol
579:3716113
447:History
439:of the
400:lesions
139:Genus:
115:Order:
103:Class:
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415:, and
367:group
337:horses
247:Genome
228:cattle
200:, and
1631:80935
1414:S2CID
1295:S2CID
1257:S2CID
973:S2CID
353:Aedes
224:sheep
186:(CVV)
65:Realm
58:Virus
1626:NCBI
1585:NCBI
1577:P5FR
1494:PMID
1406:PMID
1347:PMID
1249:PMID
1208:PMID
1170:OCLC
1160:ISBN
1124:PMID
1068:PMID
1022:PMID
965:PMID
930:PMID
889:PMID
840:PMID
784:PMID
723:PMID
674:PMID
625:PMID
584:PMID
498:ISBN
363:and
351:and
341:deer
234:and
226:and
1572:CoL
1484:PMC
1476:doi
1396:doi
1337:doi
1287:doi
1239:doi
1200:doi
1114:PMC
1106:doi
1058:doi
1054:336
1012:PMC
1004:doi
957:doi
920:doi
916:279
879:PMC
871:doi
830:PMC
820:doi
774:PMC
766:doi
713:PMC
705:doi
664:PMC
656:doi
615:doi
574:PMC
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