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Tytuł pozycji:

Analysis of Simian Hemorragic Fever Virus Proteins and the Host Cell Responses of Disease Resistant and Susceptible Primates

Tytuł :
Analysis of Simian Hemorragic Fever Virus Proteins and the Host Cell Responses of Disease Resistant and Susceptible Primates
Autorzy :
Vatter, Heather
Pokaż więcej
Index Terms :
Simian hemorrhagic fever virus (SHFV)
Arterivirus replication
Pro-inflammatory cytokines
Interleukin-10 (IL-10)
Infectious clone
Minor structural proteins
text
Wydawca :
ScholarWorks @ Georgia State University 2013-04-15T07:00:00Z
Typ dokumentu :
Zasób elektroniczny
URL :
http://scholarworks.gsu.edu/biology_diss/128
http://scholarworks.gsu.edu/cgi/viewcontent.cgi?article=1132&context=biology_diss
Dostępność :
Open access content. Open access content
Uwaga :
application/pdf
Pozostałe numery :
GSU oai:scholarworks.gsu.edu:biology_diss-1132
867774037
Źródło wspomagające :
GEORGIA STATE UNIV
From OAIster®, provided by the OCLC Cooperative.
Numer akcesji :
edsoai.ocn867774037
Zasób elektroniczny
African monkey species are natural hosts of simian hemorrhagic fever virus (SHFV) and develop persistent, asymptomatic infections. SHFV was previously shown to also cause a rapid onset fatal hemorrhagic fever disease in macaques. Infection of macaques with a new isolate of SHFV from persistently infected baboon sera, that showed high nucleotide identity with the lab strain LVR, resulted in viremia, pro-inflammatory cytokine and tissue factor production, and symptoms of coagulation defects. Primary macrophages and myeloid dendritic cell cultures from disease-susceptible macaques efficiently replicated SHFV and produced pro-inflammatory cytokines, including IL-6 and TNF-α, as well as tissue factor. Cells from disease resistant baboons produced low virus yields and the immunomodulatory cytokine IL-10. IL-10 treatment of macaque cells decreased IL-6 levels but had no effect on TNF-α levels, tissue factor or virus production suggesting that IL-10 plays a role in modulating immunopathology in disease-resistant baboons but not in regulating the efficiency of virus replication. SHFV is a member of the family Arteriviridae. The SHFV genome encodes 8 minor structural proteins. Other arteriviruses encode 4 minor structural proteins. Amino acid sequence comparisons suggest that the four additional SHFV minor structural proteins resulted from gene duplication. A full-length infectious clone of SHFV was constructed and produced virus with replication kinetics comparable to the parental virus. Mutant infectious clones, each with the start codon of one of the minor structural proteins substituted, were analyzed. All eight SHFV proteins were required for infectious virus production. The SHFV nonstructural polyprotein is processed into the mature replicase proteins by several viral proteases including papain-like cysteine proteases (PLPs). Only one or two PLP domains are present in other arteriviruses but SHFV has three PLP domains. Analysis of in vitro proteolytic processing of C- a

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