Most Alphaviruses Share a Conserved Epitopic Region on Their Nucleocapsid Protein

Greiser‐Wilke, I.; Moennig, V.; Kaaden, Oskar‐Rüger; Figueiredo, Luíz Tadeu Moraes

doi:10.1099/0022-1317-70-3-743

Cited by 49 publications

(40 citation statements)

References 29 publications

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“…These findings are in agreement with those of others that determinants recognized by neutralizing antibodies on the membrane proteins of SFV (Greiser-Wilke et al, 1989;Wust et al, 1989) and Sindbis virus (Roehrig et al, 1982;Stanley et al, 1985) are conformational. Furthermore, most epitopes on protein antigens are of a discontinuous nature (Benjamin et al, 1984) and the frequency of peptide-reactive antibodies is low after immunization with native protein (Jemmerson, 1987).…”

Section: Discussionsupporting

confidence: 82%

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Snijders

Benaissa-Trouw

Oosterlaken

et al. 1991

Journal of General Virology

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Semliki Forest virus (SFV) infection of mice was used as a model to study the applicability of synthetic peptides containing only linear epitopes as viral vaccines. The identification of linear epitopes with vaccine potential on the E2 membrane protein of SFV was based on the binding of SFV-specific antibodies to a set of overlapping synthetic hexapeptides (Pepscan) representing the whole E2 amino acid sequence. The 14 available E2-specific monoclonal antibodies which were protective in vivo proved to be unsuitable for the identification of linear epitopes because they recognized only conformational epitopes, as indicated by their lack of reactivity with unfolded, reduced E2 protein on immunoblots. Three epitopes were detected with polyclonal anti-SFV serum at amino acid positions 135 to 141,177 to 185 and 240 to 246 of the E2 protein. Synthetic peptides containing these epitopes were coupled to a carrier protein and tested as a vaccine. Mice immunized with the peptide containing amino acids 240 to 255 of protein E2 were protected against a challenge with virulent SFV but protection of mice immunized with the peptides containing amino acids 126 to 141 or 178 to 186 was only marginally better than that of controls. The prechallenge sera of most peptide-immunized mice reacted with SFVinfected cells but none of these sera neutralized the virus in vitro. However, protection of mice correlated well with SFV-specific antibody titre, suggesting antibody-mediated protection.

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Section: Discussionsupporting

confidence: 82%

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Snijders

Benaissa-Trouw

Oosterlaken

et al. 1991

Journal of General Virology

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“…For example, when monoclonal antibodies generated against the Semliki Forest Virus nucleocapsid are used in antibody capture assays, they cross-react with members of the Semliki Forest virus, WEEV, EEEV, Middelburg virus, and Ndumu virus complexes but do not cross-react at all with VEEV or Barmah Forest virus (17). As the nucleocapsid is one of the more conserved virion proteins, this may reflect some ancient relationships among the alphaviruses.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary Relationships and Systematics of the Alphaviruses

Powers

Brault

Shirako

et al. 2001

J Virol

342

287

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Partial E1 envelope glycoprotein gene sequences and complete structural polyprotein sequences were used to compare divergence and construct phylogenetic trees for the genus Alphavirus. Tree topologies indicated that the mosquito-borne alphaviruses could have arisen in either the Old or the New World, with at least two transoceanic introductions to account for their current distribution. The time frame for alphavirus diversification could not be estimated because maximum-likelihood analyses indicated that the nucleotide substitution rate varies considerably across sites within the genome. While most trees showed evolutionary relationships consistent with current antigenic complexes and species, several changes to the current classification are proposed. The recently identified fish alphaviruses salmon pancreas disease virus and sleeping disease virus appear to be variants or subtypes of a new alphavirus species. Southern elephant seal virus is also a new alphavirus distantly related to all of the others analyzed. Tonate virus and Venezuelan equine encephalitis virus strain 78V3531 also appear to be distinct alphavirus species based on genetic, antigenic, and ecological criteria. Trocara virus, isolated from mosquitoes in Brazil and Peru, also represents a new species and probably a new alphavirus complex.

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“…The antibodies used against the following antigens are indicated in parentheses: GAPDH (SC-51906; Santa Cruz) and IRF3 for immunofluorescence analysis (IFA; 550428; BD Biosciences); IRF3 for immunoblotting (SC-9082; Santa Cruz); and Ser398 phospho-IRF3 (07-581; Millipore), eIF2␣ (SC-11386; Santa Cruz), Ser51 phospho-eIF2␣ (9721; Cell Signaling), PKR (SC-707; Santa Cruz), and Thr446 phospho-PKR (1120-1; Epitomics). Puromycin was as described previously (77), dsRNA (clone K1) was obtained from English and Scientific Consulting, ISG56 was kindly provided by Ganes Sen, Viperin was kindly provided by Peter Cresswell, and Alphavirus capsid was kindly provided by Irene Greiser-Wilke (38).…”

Section: Methodsmentioning

confidence: 99%

Chikungunya Virus Induces IPS-1-Dependent Innate Immune Activation and Protein Kinase R-Independent Translational Shutoff

White

Sali

Alvarado

et al. 2011

J Virol

116

125

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Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the Indian Ocean. Despite the current and potential danger posed by this virus, we know surprisingly little about the induction and evasion of CHIKV-associated antiviral immune responses. With this in mind we investigated innate immune reactions to CHIKV in human fibroblasts, a demonstrable in vivo target of virus replication and spread. We show that CHIKV infection leads to activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent transcription of IRF3-dependent antiviral genes, including beta interferon (IFN-␤). IRF3 activation occurs by way of a virus-induced innate immune signaling pathway that includes the adaptor molecule interferon promoter stimulator 1 (IPS-1). Despite strong transcriptional upregulation of these genes, however, translation of the corresponding proteins is not observed. We further demonstrate that translation of cellular (but not viral) genes is blocked during infection and that although CHIKV is found to trigger inactivation of the translational molecule eukaryotic initiation factor subunit 2␣ by way of the double-stranded RNA sensor protein kinase R, this response is not required for the block to protein synthesis. Furthermore, overall diminution of cellular RNA synthesis is also observed in the presence of CHIKV and transcription of IRF3-dependent antiviral genes appears specifically blocked late in infection. We hypothesize that the observed absence of IFN-␤ and antiviral proteins during infection results from an evasion mechanism exhibited by CHIKV that is dependent on widespread shutoff of cellular protein synthesis and a targeted block to late synthesis of antiviral mRNA transcripts. Tanzania in 1953 (52, 69). The virus causes an acute febrile illness associated with severe joint pain that can persist long after viral clearance (9,26,42,47,49,62,68,75). In 2005 and 2006 CHIKV reemerged on a number of Indian Ocean islands and subsequently in India in 2006 and 2007 (78). Since these locations are popular tourist destinations, such outbreaks represent significant threats to European countries from travelerassociated infections. Because the virus is transmitted most commonly via mosquitoes (23, 67), changing patterns of vector distribution and abundance in response to climate change (36) and increased vector-human contact following human encroachment into undeveloped areas renders CHIKV an emerging pathogen of high potential danger for future generations. Unfortunately, information regarding many basic aspects of CHIKV molecular biology, immunology, and pathology are lacking. Chikungunya virus (CHIKV) was first isolated inCHIKV is a member of the family Togaviridae and genus Alphavirus. The enveloped virion contains an icosahedral nucleocapsid and an ϳ12-kb plus-strand single-stranded RNA genome that includes a 5Ј cap and 3Ј polyadenylation. The genome includes two open reading frames (ORFs) separately encoding polyproteins th...

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Most Alphaviruses Share a Conserved Epitopic Region on Their Nucleocapsid Protein

Cited by 49 publications

References 29 publications

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Evolutionary Relationships and Systematics of the Alphaviruses

Chikungunya Virus Induces IPS-1-Dependent Innate Immune Activation and Protein Kinase R-Independent Translational Shutoff

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