The E residue is located in domain I of the Env protein; this residue is conserved within the JEV serocomplex but not among other flaviviruses. Consequently, after inoculating the viruses into mice, the EK virus was quickly eliminated from serum through binding to GAG found on extracellular matrices and cell surfaces , resulting in inefficient dissemination and virulence attenuation The furin-mediated internal cleavage of prM is required for flavivirus virion infectivity.
Flaviviruses share conserved basic residues at positions P1, P2, and P4 for the recognition of furin at the prM cleavage site; basic residues at positions P3, P5, and P6 of the substrate also are preferred for furin cleavage 2. The prM S90R mutation is located at the P3 position of the cleavage site that potentially could improve the prM cleavage. A previous study of DENV-2 showed that a decrease in prM cleavage was associated with higher proportions of subviral particles and prM-containing virions in culture medium 11 , Flavivirus 2K peptide consists of 23 amino acids and spans the ER membrane, with its N- and C-terminal tails on the cytoplasmic and ER lumen sides, respectively The regulated cleavages at the NS4a-2K-NS4b junctions are critical for the rearrangement of cytoplasmic membrane 26 , In Kunjin virus, the individual expression of NS4a-2K resulted in membrane rearrangement that mostly resembled a virus-induced structure, while the removal of the 2K peptide led to a less profound membrane rearrangement Although the exact function of 2K peptide remains to be determined, its role in RNA replication was indicated by the results that V9M mutation in 2K conferred on WNV to overcome the exclusion of superinfection Fig.
These results suggest that the 2K mutation modulates the ER membrane rearrangement, leading to a better scaffold for replication complex formation. Along the same lines, the NS4a KR mutation was mapped to the P3 position of the NS4a-2K cleavage site; although the KR substitution is a minor side chain change, it may affect the cleavage efficiency, facilitating membrane rearrangement and replication complex formation.
In addition, NS4a mutation may affect its interaction with host factors to overcome the exclusion of superinfection. Experiments are ongoing to dissect these potential mechanisms.
The results indicate that superinfection exclusion was not due to any changes of host factors during the selection of replicon cells; instead, the exclusion was due to the presence of replicon RNAs and proteins. It is possible that the preestablished replication of replicon has used up the host factors e. However, the 2K mutation and, to a less degree, the NS4a mutation could not only overcome the exclusion of superinfection but also could suppress the preestablished replicon replication.
In contrast, incubating the replicon-containing cells with the WT WNV did not significantly suppress the replicon replication Fig. These results support the idea that superinfection exclusion is a result of competition for intracellular host factors. It remains to be determined how the mutant 2K scavenges the host factors that already have been recruited to the preestablished replication complex.
National Center for Biotechnology Information , U. Journal List J Virol v. J Virol. Published online Sep 2. Kristen A. Author information Article notes Copyright and License information Disclaimer.
Present address: 10 Biopolis Rd. Phone: 65 Fax: 65 E-mail: moc. Received Jun 12; Accepted Aug This article has been cited by other articles in PMC. Abstract Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Open in a separate window. Plasmid construction. Viral attachment and entry assays. Transient replicon assay. VLP assay. Viral growth kinetics and plaque assay.
Selection and sequencing of superinfection-competent WNV. Exclusion of superinfection through suppression of viral RNA synthesis. Mutations in both structural and nonstructural genes are responsible for superinfection competency. Best, S. Morris, J. Shannon, S. Robertson, D. Mitzel, G. Park, E. Boer, J. Wolfinbarger, and M. Chambers, T. Hahn, R. Galler, and C. Flavivirus genome organization, expression, and replication.
Chen, L. Lin, C. Liao, C. Lin, Y. Huang, C. Yeh, S. Lai, J. Jan, and C. Generation and characterization of organ-tropism mutants of Japanese encephalitis virus in vivo and in vitro.
Virology : Christen, L. Seto, and E. Superinfection exclusion of vaccinia virus in virus-infected cell cultures. Claus, C. Tzeng, U.
Liebert, and T. Rubella virus-induced superinfection exclusion studied in cells with persisting replicons. Diamond, M. Zachariah, and E. Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA. Ellenberg, P. Linero, and L. Superinfection exclusion in BHK cells persistently infected with Junin virus. Geib, T.
Sauder, S. Venturelli, C. Hassler, P. Staeheli, and M. Selective virus resistance conferred by expression of Borna disease virus nucleocapsid components. Gubler, D. Kuno, and L. Flaviviruses, p. Knipe and P. Howley ed. Guo, J. Hayashi, and C. West Nile virus inhibits the signal transduction pathway of alpha interferon.
Junjhon, J. Lausumpao, S. Supasa, S. Noisakran, A. Songjaeng, P. Saraithong, K. Chaichoun, U. Utaipat, P. Keelapang, A. Kanjanahaluethai, C. Puttikhunt, W. Kasinrerk, P. Malasit, and N. Virus taxonomy: classification and nomenclature of viruses. Elsevier Inc. Moreover, in the last decade novel insect-specific viruses, which are host-restricted to replication in invertebrate cells, were discovered in mosquitoes. These viruses phylogenetically affiliate with mosquito-borne flaviviruses MBFV despite their apparent insect-restricted phenotype.
Insect-specific viruses detected in laboratory mosquito colonies and their potential implications for experiments evaluating arbovirus vector competence. Am J Trop Med Hyg. Superinfection exclusion SIE is the process by which host cells infected with one virus do not support productive replication of the same or similar virus. Superinfection exclusion in cells infected with hepatitis C virus.
J Virol [Internet]. SIE assays with MBFV and ISFV have been performed in order to establish a preventative intervention strategy for blocking the transmission of agents of human diseases and in order to gain a better understanding of any additional factor s that could alter vector competence of mosquitoes in both enzootic and epizootic transmission cycles.
In this sense, different in vivo and in vitro studies have assessed the relative potential of different ISFV to interfere with replication of flaviviruses of human health importance. Transmission of West Nile virus by Culex quinquefasciatus say infected with Culex flavivirus izabal. Transmission dynamics of an insect-specific flavivirus in a naturally infected Culex pipiens laboratory colony and effects of co-infection on vector competence for West Nile virus.
A new insect-specific Flavivirus from northern Australia suppresses replication of West Nile virus and Murray Valley Encephalitis virus in co-infected mosquito cells. PLoS One. Potential for co-infection of a mosquito-specific Flavivirus, Nhumirim virus, to block West Nile virus transmission in mosquitoes. Analysis of mosquito-borne Flavivirus superinfection in Culex tritaeniorhynchus Diptera: Culicidae cells persistently infected with Culex flavivirus Flaviviridae.
J Med Entomol. Historical, epidemiological and ecological aspects of arboviruses in Argentina: Flaviviridae, Bunyaviridae and Rhabdoviridae. An overview of arbovirology in Brazil and neighbouring countries.
West Nile virus isolation from equines in Argentina, Emerg Infect Dis. Vector-Borne Zoonotic Dis. Since , Argentina has experienced the re-emergence of DENV, which represented a growing public health problem. Concerning WNV circulation, this virus was isolated in from the brains of three dead horses with clinical manifestations of encephalitis in Argentina. However, the impact on animal and human public health was considerably lower than in the Northern hemisphere.
Insect-specific viruses detected in laboratory mosquito colonies and their potential implications for experiments evaluating arbovirus vector competence.
Am J Trop Med Hyg. Superinfection exclusion in cells infected with hepatitis C virus. J Virol [Internet]. Transmission of West Nile virus by Culex quinquefasciatus say infected with Culex flavivirus izabal. Transmission dynamics of an insect-specific flavivirus in a naturally infected Culex pipiens laboratory colony and effects of coinfection on vector competence for West Nile virus.
A new insect-specific Flavivirus from northern Australia suppresses replication of West Nile virus and Murray Valley Encephalitis virus in co-infected mosquito cells.
PLoS One. Potential for co-infection of a mosquito-specific Flavivirus, Nhumirim virus, to block West Nile virus transmission in mosquitoes. Analysis of mosquito-borne Flavivirus superinfection in Culex tritaeniorhynchus Diptera: Culicidae cells persistently infected with Culex flavivirus Flaviviridae.
J Med Entomol. Historical, epidemiological and ecological aspects of arboviruses in Argentina: Flaviviridae, Bunyaviridae and Rhabdoviridae. An overview of arbovirology in Brazil and neighbouring countries. West Nile virus isolation from equines in Argentina, Emerg Infect Dis. Vector-Borne Zoonotic Dis. West Nile virus in the New World: trends in the spread and proliferation of West Nile virus in the Western hemisphere.
Zoonoses Public Health. New strains of Culex flavivirus isolated in Argentina. J Med Entomol [Internet]. Dengue virus: isolation, propagation, quantification, and storage.
The preestablished replication of the replicon could be suppressed by infecting the cells with the 2K mutant WNV but not with the wild-type virus. These results suggest that WNV superinfection exclusion is a result of competition for intracellular host factors that are required for viral RNA synthesis.
N2 - Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. AB - Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Overview Fingerprint.
0コメント