A second RGD motif in the 1D capsid protein of a SAT1 type foot-and-mouth disease virus field isolate is not essential for attachment to target cells

Storey, Pamela; Theron, Jacques; Maree, Francois Frederick; O’Neill, Hester G.

doi:10.1016/j.virusres.2006.11.003

Cited by 17 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The RGD motif is a known participant in the interaction of a number of ligands with cell receptors from the integrin superfamily (8). Residues of the RGD motif, as well as RGDassociated regions, have previously been shown to influence the activity of a number of enveloped and nonenveloped viruses (4,10,11,13,15,17,21,27,36,42,44,47,49,50,52,56). Moreover, as evidence of the importance of this region, a 10-mer DENV-2 synthetic peptide sequence that overlapped the flavivirus Mut-5-like region (i.e., flavivirus amino acid residues at the Mut-5 positions) inhibited the binding of a DENV-2 domain III envelope protein to mosquito but not mammalian cells, indicating that this region has more specificity for insect cells (16).…”

Section: Discussionmentioning

confidence: 99%

Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

Pierro

Powers

Olson

2008

J Virol

View full text Add to dashboard Cite

Wild-type Sindbis virus (SINV) strain MRE16 efficiently infects Aedes aegypti midgut epithelial cells (MEC), but laboratory-derived neurovirulent SINV strain TE/52J infects MEC poorly. SINV determinants for MEC infection have been localized to the E2 glycoprotein. The E2 amino acid sequences of MRE16 and TE/52J differ at 60 residue sites. To identify the genetic determinants of MEC infection of MRE16, the TE/52J virus genome was altered to contain either domain chimeras or more focused nucleotide substitutions of MRE16. The growth patterns of derived viruses in cell culture were determined, as were the midgut infection rates (MIR) in A. aegypti mosquitoes. The results showed that substitutions of MRE16 E2 aa 95 to 96 and 116 to 119 into the TE/52J virus increased MIR both independently and in combination with each other. In addition, a unique PPF/.GDS amino acid motif was located between these two sites that was found to be a highly conserved sequence among alphaviruses and flaviviruses but not other arboviruses.The majority of medically important mosquito-borne alphaviruses (family Togaviridae) and flaviviruses (family Flaviviridae) are vectored by two Culicinae mosquito genera, Aedes and Culex. The mosquito Aedes aegypti is a major vector in the epidemic disease cycles of the flaviviruses dengue virus (DENV) and yellow fever virus, as well as being a competent vector for a number of alphaviruses, including the prototypic alphavirus Sindbis virus (SINV). There are three major genotypes of SINV, the Paleoarctic-Ethiopian (P/E), which is found in Europe and Africa, the Oriental-Australian (O/A), which is found in Asia and Australasia, and the Southwest genotype, which is found in the southwestern region of Western Australia (28,34,40,41). SINV strain MRE16 is an O/A genotype isolated between 1966 and 1969 from a pool of Culex tritaeniorhynchus mosquitoes in Malaysia (20a). A full-length infectious clone (IC) of MRE16 has been generated, and it is currently the model O/A genotype being investigated in laboratory mosquito infection assays (24,25,29,31,43). MRE16 was previously found to have a midgut infection rate (MIR) in A. aegypti mosquitoes of 100% at 7 days postinfection (dpi) (24). In contrast, recombinant SINV strain TE/5Ј2J (P/E genotype), a double subgenomic SINV constructed from a chimeric mouse neurovirulent variant of SINV AR339 called TE12, infects less than 15% of A. aegypti mosquito midguts when analyzed similarly (31).The MRE16 E2 gene has been implicated as having genetic determinants of midgut infection (31). Sequence comparison between the SINV TE/5Ј2J and MRE16 E2 genes identified approximately 316 nucleotide (nt) (24.9%) and 60 amino acid (aa) residue (14.2%) differences (43). In this work, SINV strain TE/5Ј2J was mutated to generate viruses containing MRE16 sequences within the E2 gene (as either chimeras or point mutations) and the viruses were evaluated for the ability to productively infect the MEC of A. aegypti mosquitoes. The data demonstrated that TE/5Ј2J viruses having the specific MRE1...

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

Pierro

Powers

Olson

2008

J Virol

View full text Add to dashboard Cite

show abstract

“…Baby hamster kidney-21 cells (BHK-21, ATCC CCL-10) were maintained and propagated in Eagle's basal medium (BME; Life Technologies) as described previously (27) MAb isolation. Monoclonal antibodies (MAbs) were prepared by inoculating BALB/c mice with a blend of inactivated and purified 146S particles of SAT1/Kenya (KEN)/11/2005, SAT/2/ZIM/5/81, and SAT3/ ZIM/4/81.…”

Section: Methodsmentioning

confidence: 99%

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Opperman

Rotherham

Esterhuysen

et al. 2014

J Virol

View full text Add to dashboard Cite

Monoclonal-antibody (MAb)-resistant mutants were used to map antigenic sites on foot-and-mouth disease virus (FMDV), which resulted in the identification of neutralizing epitopes in the flexible ␤G-␤H loop in VP1. For FMDV SAT2 viruses, studies have shown that at least two antigenic sites exist. By use of an infectious SAT2 cDNA clone, 10 structurally exposed and highly variable loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of SAT2/Zimbabwe (ZIM)/ 7/83 (topotype II) and replaced with the corresponding regions of SAT2/Kruger National Park (KNP)/19/89 (topotype I). Virus neutralization assays using convalescent-phase antisera raised against the parental virus, SAT2/ZIM/7/83, indicated that the mutant virus containing the TQQS-to-ETPV mutation in the N-terminal part of the ␤G-␤H loop of VP1 showed not only a significant increase in the neutralization titer but also an increase in the index of avidity to the convalescent-phase antisera. Furthermore, antigenic profiling of the epitope-replaced and parental viruses with nonneutralizing SAT2-specific MAbs led to the identification of two nonneutralizing antigenic regions. Both regions were mapped to incorporate residues 71 to 72 of VP2 as the major contact point. The binding footprint of one of the antigenic regions encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 48 to 50 of VP1, and the second antigenic region encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 84 to 86 and 109 to 11 of VP1. This is the first time that antigenic regions encompassing residues 71 to 72 of VP2 have been identified on the capsid of a SAT2 FMDV. IMPORTANCEMonoclonal-antibody-resistant mutants have traditionally been used to map antigenic sites on foot-and-mouth disease virus (FMDV). However, for SAT2-type viruses, which are responsible for most of the FMD outbreaks in Africa and are the most varied of all seven serotypes, only two antigenic sites have been identified. We have followed a unique approach using an infectious SAT2 cDNA genome-length clone. Ten structurally surface-exposed, highly varied loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of the SAT2/ZIM/7/83 virus. These regions were replaced with the corresponding regions of an antigenically disparate virus, SAT2/KNP/19/89. Antigenic profiling of the epitope-replaced and parental viruses with SAT2-specific MAbs led to the identification of two unique antibody-binding footprints on the SAT2 capsid. In this report, evidence for the structural engineering of antigenic sites of a SAT2 capsid to broaden cross-reactivity with antisera is provided. Genetically modified viruses provide a valuable tool for the manipulation of the biological properties of field and laboratory strains and present a promising avenue for the design of safe and effective vaccines. The modification of antigenic regions of human immunodeficiency virus (HIV) by amino acid (aa) substitutions in a recombinant virus has been used to confirm m...

show abstract

“…The introduction of specific mutations into the cloned genomes of viruses has allowed the manipulation of the biological prop-erties of field and laboratory strains and presents a promising avenue for the design of safe and effective vaccines [28][29][30]. We have structurally-engineered recombinant SAT viruses, containing desirable antigenic determinants and cell adaptation phenotypes [28,31,32] providing the proof-of-concept to rationally design viruses with the desired biological properties of a good vaccine strain. Several studies have shown that inter-serotype chimeric vaccines successfully induce protective immune responses and protect FMD host species against live virus challenge [26,30,33].…”

Section: Introductionmentioning

confidence: 99%

Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge

Maree

Nsamba

Mutowembwa

et al. 2015

Vaccine

View full text Add to dashboard Cite

The genetic diversity of the three Southern African Territories (SAT) types of foot-and-mouth disease virus (FMDV) reflects high antigenic variation, and indications are that vaccines targeting each SATspecific topotype may be needed. This has serious implications for control of FMD using vaccines as well as the choice of strains to include in regional antigen banks. Here, we investigated an intra-serotype chimeric virus, vSAT2 ZIM14 -SAT2, which was engineered by replacing the surface-exposed capsid-coding region (1B-1D/2A) of a SAT2 genome-length clone, pSAT2, with that of the field isolate, SAT2/ZIM/14/90. The chimeric FMDV produced by this technique was viable, grew to high titres and stably maintained the 1B-1D/2A sequence upon passage. Chemically inactivated, oil adjuvanted vaccines of both the chimeric and parental immunogens were used to vaccinate cattle. The serological response to vaccination showed the production of strong neutralizing antibody titres that correlated with protection against homologous FMDV challenge. We also predicted a good likelihood that cattle vaccinated with an intra-serotype chimeric vaccine would be protected against challenge with viruses that caused recent outbreaks in southern Africa. These results provide support that chimeric vaccines containing the external capsid of field isolates induce protective immune responses in FMD host species similar to the parental vaccine.

show abstract

A second RGD motif in the 1D capsid protein of a SAT1 type foot-and-mouth disease virus field isolate is not essential for attachment to target cells

Abstract: The amino acid sequence motif Arg-Gly-Asp (RGD), located in the surface-exposed βG-βH loop of the 1D protein of different serotypes and subtypes of foot-and-mouth disease

Cited by 17 publications

References 37 publications

Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

Genetic Determinants of Sindbis Virus Mosquito Infection Are Associated with a Highly Conserved Alphavirus and Flavivirus Envelope Sequence

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge

Contact Info

Product

Resources

About