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RNA-binding region of Macrobrachium rosenbergii nodavirus capsid protein

Goh ZH, Mohd NAS, Tan SG, Bhassu S, Tan WS

J Gen Virol, 2014 Sep;95(Pt 9):1919-1928.
PMID: 24878641 DOI: 10.1099/vir.0.064014-0

White tail disease (WTD) kills prawn larvae and causes drastic losses to the freshwater prawn (Macrobrachium rosenbergii) industry. The main causative agent of WTD is Macrobrachium rosenbergii nodavirus (MrNV). The N-terminal end of the MrNV capsid protein is very rich in positively charged amino acids and is postulated to interact with RNA molecules. N-terminal and internal deletion mutagenesis revealed that the RNA-binding region is located at positions 20-29, where 80 % of amino acids are positively charged. Substitution of all these positively charged residues with alanine abolished the RNA binding. Mutants without the RNA-binding region still assembled into virus-like particles, suggesting that this region is not a part of the capsid assembly domain. This paper is, to the best of our knowledge, the first to report the specific RNA-binding region of MrNV capsid protein.

Matched MeSH terms: Capsid Proteins/biosynthesis*; Capsid Proteins/genetics*; Capsid Proteins/metabolism
High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1

Tan CS, Cardosa MJ

Arch Virol, 2007;152(6):1069-73.
PMID: 17318736

Human enterovirus 71 has emerged as an important pathogen of children in the Asia Pacific region, and it may be important to consider the development of a vaccine against this virus. Human cord serum was used as a source of neutralizing antibodies to determine whether the N- or C-terminal half of the VP1 capsid protein was more likely to harbour neutralizing determinants. Cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect ELISA against recombinant VP1 antigen as well as the N- and C-terminal portions of VP1 antigen. High-titred human neutralizing antibodies were significantly more reactive with the N-terminal half of VP1 than weak or negative sera. The N-terminal half of human enterovirus 71 is likely to have important neutralizing antibody determinants and should be investigated further in vaccine development efforts.

Matched MeSH terms: Capsid Proteins/genetics; Capsid Proteins/immunology*; Capsid Proteins/chemistry
Fulltext Molecular characterization of the viral structural protein genes in the first outbreak of dengue virus type 2 in Hunan Province, inland China in 2018

Guan J, He Z, Qin M, Deng X, Chen J, Duan S, et al.

BMC Infect Dis, 2021 Feb 10;21(1):166.
PMID: 33568111 DOI: 10.1186/s12879-021-05823-3

BACKGROUND: An unexpected dengue outbreak occurred in Hunan Province in 2018. This was the first dengue outbreak in this area of inland China, and 172 cases were reported.
METHODS: To verify the causative agent of this outbreak and characterise the viral genes, the genes encoding the structural proteins C/prM/E of viruses isolated from local residents were sequenced followed by mutation and phylogenetic analysis. Recombination, selection pressure, potential secondary structure and three-dimensional structure analyses were also performed.
RESULTS: Phylogenetic analysis revealed that all epidemic strains were of the cosmopolitan DENV-2 genotype and were most closely related to the Zhejiang strain (MH010629, 2017) and then the Malaysia strain (KJ806803, 2013). Compared with the sequence of DENV-2SS, 151 base substitutions were found in the sequences of 89 isolates; these substitutions resulted in 20 non-synonymous mutations, of which 17 mutations existed in all samples (two in the capsid protein, six in the prM/M proteins, and nine in the envelope proteins). Moreover, amino acid substitutions at the 602nd (E322:Q → H) and 670th (E390: N → S) amino acids may have enhanced the virulence of the epidemic strains. One new DNA binding site and five new protein binding sites were observed. Two polynucleotide binding sites and seven protein binding sites were lost in the epidemic strains compared with DENV-2SS. Meanwhile, five changes were found in helical regions. Minor changes were observed in helical transmembrane and disordered regions. The 429th amino acid of the E protein switched from a histamine (positively charged) to an asparagine (neutral) in all 89 isolated strains. No recombination events or positive selection pressure sites were observed. To our knowledge, this study is the first to analyse the genetic characteristics of epidemic strains in the first dengue outbreak in Hunan Province in inland China.
CONCLUSIONS: The causative agent is likely to come from Zhejiang Province, a neighbouring province where dengue fever broke out in 2017. This study may help clarify the intrinsic geographical relatedness of DENV-2 and contribute to further research on pathogenicity and vaccine development.

Matched MeSH terms: Capsid Proteins/genetics; Capsid Proteins/metabolism; Capsid Proteins/chemistry
Fulltext Molecular characterisation of grouper iridovirus isolates from Peninsular Malaysia

Hassan, M.D., Hazeri, M., Omar, A.R., Abba, Y., Allaudin, Z.N., Soltani, M., et al.

Jurnal Veterinar Malaysia, 2017;29(1):1-6.
MyJurnal

Grouper Iriovirus (GIV) is one of the most devastating viral diseases of marine and cultured groupers worldwide. In the current study, 5 presumptive Malaysian GIV isolates were characterised through PCR amplification of the major capsid protein (MCP) gene and phylogenetic analysis of the sequences. The sequences from the five GIV isolates showed 100% homology with each other and a close relationship with grouper iridovirus isolate (GIV_Tn_352), which was clustered in group 1 together with King grouper iridovirus isolate (KGIV_Cy_346), Singapore grouper iridovirus (SGIV), and Crimson snapper iridovirus isolate (CSIV). The phylogenetic tree also showed different degree of relatedness with other Ranavirus strains which were obtained from the blast of GIV MCP gene in the NCBI database. This study confirmed the GIV isolates from Malaysia are related to other isolates that were reported previously.

Matched MeSH terms: Capsid Proteins
Fulltext Electrostatic interactions at the five-fold axis alter heparin-binding phenotype and drive enterovirus A71 virulence in mice

Tee HK, Tan CW, Yogarajah T, Lee MHP, Chai HJ, Hanapi NA, et al.

PLoS Pathog, 2019 11;15(11):e1007863.
PMID: 31730673 DOI: 10.1371/journal.ppat.1007863

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease epidemics with neurological complications and fatalities. However, the neuropathogenesis of EV-A71 remains poorly understood. In mice, adaptation and virulence determinants have been mapped to mutations at VP2-149, VP1-145 and VP1-244. We investigate how these amino acids alter heparin-binding phenotype and shapes EV-A71 virulence in one-day old mice. We constructed six viruses with varying residues at VP1-98, VP1-145 (which are both heparin-binding determinants) and VP2-149 (based on the wild type 149K/98E/145Q, termed KEQ) to generate KKQ, KKE, KEE, IEE and IEQ variants. We demonstrated that the weak heparin-binder IEE was highly lethal in mice. The initially strong heparin-binding IEQ variant acquired an additional mutation VP1-K244E, which confers weak heparin-binding phenotype resulting in elevated viremia and increased virus antigens in mice brain, with subsequent high virulence. IEE and IEQ-244E variants inoculated into mice disseminated efficiently and displayed high viremia. Increasing polymerase fidelity and impairing recombination of IEQ attenuated the virulence, suggesting the importance of population diversity in EV-A71 pathogenesis in vivo. Combining in silico docking and deep sequencing approaches, we inferred that virus population diversity is shaped by electrostatic interactions at the five-fold axis of the virus surface. Electrostatic surface charges facilitate virus adaptation by generating poor heparin-binding variants for better in vivo dissemination in mice, likely due to reduced adsorption to heparin-rich peripheral tissues, which ultimately results in increased neurovirulence. The dynamic switching between heparin-binding and weak heparin-binding phenotype in vivo explained the neurovirulence of EV-A71.

Matched MeSH terms: Capsid Proteins/genetics; Capsid Proteins/metabolism*; Capsid Proteins/chemistry
Fulltext Detection and genetic characterization of canine astroviruses in pet dogs in Guangxi, China

Zhou H, Liu L, Li R, Qin Y, Fang Q, Balasubramaniam VR, et al.

Virol J, 2017 08 17;14(1):156.
PMID: 28814340 DOI: 10.1186/s12985-017-0823-4

BACKGROUND: Astroviruses (AstVs) have been reported to infect and cause gastroenteritis in most animal species. Human AstVs were regarded the causative agent of viral diarrhea in children. In dogs, little is known about the epidemiology and clinical significance of AstV infection.
FINDINGS: In this study, we collected and tested 253 rectal swabs from pet dogs; of which 64 samples (25.3%) tested positive for AstVs with diarrhea and 15 more samples (5.9%) also was identified as AstVs, however without any clinical signs. Phylogenetic analysis of 39 partial ORF1b sequences from these samples revealed that they are similar to AstVs, which can be subdivided into three lineages. Interestingly, out of the 39 isolates sequenced, 16 isolates are shown to be in the Mamastrovirus 5/canine astrovirus (CAstV) lineage and the remaining 23 isolates displayed higher similarities with known porcine astrovirus (PoAstV) 5 and 2. Further, analysis of 13 capsid sequences from these isolates showed that they are closely clustered with Chinese or Italy CAstV isolates.
CONCLUSIONS: The findings indicate that CAstVs commonly circulate in pet dogs, and our sequencing results have shown the genomic diversity of CAstVs leading to increasing number of clusters.

Matched MeSH terms: Capsid Proteins
Genetic variability and evolutionary analyses of the coat protein gene of Tomato mosaic virus

Rangel EA, Alfaro-Fernández A, Font-San-Ambrosio MI, Luis-Arteaga M, Rubio L

Virus Genes, 2011 Dec;43(3):435-8.
PMID: 21881940 DOI: 10.1007/s11262-011-0651-3

Tomato mosaic virus (ToMV), a member of the genus Tobamovirus, infects several ornamental and horticultural crops worldwide. In this study, the nucleotide sequences of the coat protein gene of worldwide ToMV isolates were analyzed to estimate the genetic structure and diversity of this virus and the involved evolutionary forces. The phylogenetic analysis showed three clades with high bootstrap support: Clade I contained three ToMV isolates from Brazil collected from pepper, Clade II comprised one Brazilian ToMV isolate from pepper, and Clade III was composed of ToMV isolates collected from different plant hosts (pepper, tomato, eggplant, lilac, camellia, dogwood, red spruce, etc.) and water (from melting ice, lakes and streams) from different countries: USA, Brazil, Korea, Germany, Spain, Denmark (Greenland), China, Taiwan, Malaysia, Iran, and Kazakhstan. With the exception of Brazil, nucleotide diversity within and between different geographic regions was very low, although statistical analyses suggested some gene flow between most of these regions. Our analyses also suggested a strong negative selection which could have contributed to the genetic stability of ToMV.

Matched MeSH terms: Capsid Proteins/genetics*
Phylogenetic designation of enterovirus 71 genotypes and subgenotypes using complete genome sequences

Chan YF, Sam IC, AbuBakar S

Infect Genet Evol, 2010 Apr;10(3):404-12.
PMID: 19465162 DOI: 10.1016/j.meegid.2009.05.010

Human enterovirus 71 (EV-71) is genotyped for molecular epidemiological investigation mainly using the two structural genes, VP1 and VP4. Based on these, EV-71 is divided into three genotypes, A, B and C, and within the genotypes B and C, there are further subgenotypes, B1-B5 and C1-C5. Classification using these genes is useful but gives incomplete phylogenetic information. In the present study, the phylogenetic relationships amongst all the known EV-71 and human enterovirus A (HEV-A) isolates with complete genome sequences were examined. A different tree topology involving EV-71 isolates of subgenotypes, C4 and B5 was obtained in comparison to that drawn using VP1. The nucleotide sequence divergence of the C4 isolates was 18.11% (17-20%) when compared to other isolates of subgenotype C. However, this positions the C4 isolates within the cut-off divergence value of 17-22% used to designate the virus genotypes. Hence, it is proposed here that C4 should be designated as a new genotype D. In addition, the subgenotype B5 isolates had an average nucleotide divergence of only 6.14% (4-8%) when compared to other subgenotype B4 isolates. This places the B5 isolates within the subgenotype B4. It is proposed here that the B5 isolates to be redesignated as B4. With the newly proposed genotype D and inclusion of subgenotype B5 within B4, the average nucleotide divergence between genotypes was 18.99% (17-22%). Inter- and intra-subgenotype average divergences were 12.02% (10-14%) and 3.92% (1-10%), respectively. A phylogenetic tree built using the full genome sequences is robust as it takes into consideration changes in the sequences of both the structural and non-structural genes. Similar nucleotide similarities, however, were obtained if only VP1 and 3D RNA polymerase genes were used. Furthermore, addition of 3D RNA polymerase sequences will also show recombination events. Hence, in the absence of full genome sequences, it is proposed here that a combination of VP1 and 3D RNA polymerase gene sequences be used for initial genotyping of EV-71 isolates.

Matched MeSH terms: Capsid Proteins/genetics
Mutagenesis of the nucleocapsid protein of Nipah virus involved in capsid assembly

Ong ST, Yusoff K, Kho CL, Abdullah JO, Tan WS

J Gen Virol, 2009 Feb;90(Pt 2):392-397.
PMID: 19141448 DOI: 10.1099/vir.0.005710-0

The nucleocapsid protein of Nipah virus produced in Escherichia coli assembled into herringbone-like particles. The amino- and carboxy-termini of the N protein were shortened progressively to define the minimum contiguous sequence involved in capsid assembly. The first 29 aa residues of the N protein are dispensable for capsid formation. The 128 carboxy-terminal residues do not play a role in the assembly of the herringbone-like particles. A region with amino acid residues 30-32 plays a crucial role in the formation of the capsid particle. Deletion of any of the four conserved hydrophobic regions in the N protein impaired capsid formation. Replacement of the central conserved regions with the respective sequences from the Newcastle disease virus restored capsid formation.

Matched MeSH terms: Nucleocapsid Proteins/genetics*; Nucleocapsid Proteins/ultrastructure; Capsid Proteins/genetics
Pathogenicity, sequence and phylogenetic analysis of Malaysian Chicken anaemia virus obtained after low and high passages in MSB-1 cells

Chowdhury SM, Omar AR, Aini I, Hair-Bejo M, Jamaluddin AA, Md-Zain BM, et al.

Arch Virol, 2003 Dec;148(12):2437-48.
PMID: 14648297

Specific-pathogen-free (SPF) chickens inoculated with low passage Chicken anaemia virus (CAV), SMSC-1 and 3-1 isolates produced lesions suggestive of CAV infection. Repeated passages of the isolates in cell culture until passage 60 (P60) and passage 123 produced viruses that showed a significantly reduced level of pathogenicity in SPF chickens compared to the low passage isolates. Sequence comparison indicated that nucleotide changes in only the coding region of the P60 passage isolates were thought to contribute to virus attenuation. Phylogenetic analysis indicated that SMSC-1 and 3-1 were highly divergent, but their P60 passage derivatives shared significant homology to a Japanese isolate A2.

Matched MeSH terms: Capsid Proteins/chemistry
A 12-residue epitope displayed on phage T7 reacts strongly with antibodies against foot-and-mouth disease virus

Wong CL, Yong CY, Muhamad A, Syahir A, Omar AR, Sieo CC, et al.

Appl Microbiol Biotechnol, 2018 May;102(9):4131-4142.
PMID: 29564523 DOI: 10.1007/s00253-018-8921-9

Foot-and-mouth disease (FMD) is a major threat to the livestock industry worldwide. Despite constant surveillance and effective vaccination, the perpetual mutations of the foot-and-mouth disease virus (FMDV) pose a huge challenge to FMD diagnosis. The immunodominant region of the FMDV VP1 protein (residues 131-170) displayed on phage T7 has been used to detect anti-FMDV in bovine sera. In the present study, the functional epitope was further delineated using amino acid sequence alignment, homology modelling and phage display. Two highly conserved regions (VP1145-152 and VP1159-170) were identified among different FMDV serotypes. The coding regions of these two epitopes were fused separately to the T7 genome and displayed on the phage particles. Interestingly, chimeric phage displaying the VP1159-170 epitope demonstrated a higher antigenicity than that displaying the VP1131-170 epitope. By contrast, phage T7 displaying the VP1145-152 epitope did not react significantly with the anti-FMDV antibodies in vaccinated bovine sera. This study has successfully identified a smaller functional epitope, VP1159-170, located at the C-terminal end of the structural VP1 protein. The phage T7 displaying this shorter epitope is a promising diagnostic reagent to detect anti-FMDV antibodies in vaccinated animals.

Matched MeSH terms: Capsid Proteins/genetics
First report of the infectious spleen and kidney necrosis virus (ISKNV) infection in ornamental fishes in India

Girisha SK, Kushala KB, Nithin MS, Puneeth TG, Naveen Kumar BT, Vinay TN, et al.

Transbound Emerg Dis, 2021 Mar;68(2):964-972.
PMID: 33448668 DOI: 10.1111/tbed.13793

Infectious spleen and kidney necrosis virus (ISKNV), a member of family iridoviridae, reported for the first time in a wide range of ornamental fish species in India. Significant mortalities during the year 2018-19 were reported from a number of retailers in the region with various clinical signs. The samples of moribund, dead and apparently healthy ornamental fishes were collected from retailers, located in three districts of Karnataka, India. Out of 140 fish samples, 16 samples (11.42%) representing 10 different fish species were found positive to ISKNV by OIE listed primers and same samples were reported to amplify the major capsid protein (MCP) gene of ISKNV. Further, sequence analysis of MCP gene showed that all strains detected in this study were closely related to other documented isolates from different countries with an identity ranging from 98.76% to 100%. Further, they clustered in the clade of ISKNV, during the phylogenetic analysis. The sequence similarity was high (99.94%) to ISKNV strains from Japan, Australia and Malaysia. This is the first report of an ISKNV infection in India. Moreover, out of 10 ISKNV-positive fish species, three species were reported positive to ISKNV for the first time in the world. Further, the in vitro experiment showed the growth of virus in Asian sea bass cell line, which is a natural host of ISKNV. Therefore, considering the lethal nature of megalocytiviruses to infect a vast range of species, proper biosecurity measures need to be taken to control these emerging pathogens.

Matched MeSH terms: Capsid Proteins/genetics
Virus-like nanoparticles as a novel delivery tool in gene therapy

Jeevanandam J, Pal K, Danquah MK

Biochimie, 2019 Feb;157:38-47.
PMID: 30408502 DOI: 10.1016/j.biochi.2018.11.001

Viruses are considered as natural nanomaterials as they are in the size range of 20-500 nm with a genetical material either DNA or RNA, which is surrounded by a protein coat capsid. Recently, the field of virus nanotechnology is gaining significant attention from researchers. Attention is given to the utilization of viruses as nanomaterials for medical, biotechnology and energy applications. Removal of genetic material from the viral capsid creates empty capsid for drug incorporation and coating the capsid protein crystals with antibodies, enzymes or aptamers will enhance their targeted drug deliver efficiency. Studies reported that these virus-like nanoparticles have been used in delivering drugs for cancer. It is also used in imaging and sensory applications for various diseases. However, there is reservation among researchers to utilize virus-like nanoparticles in targeted delivery of genes in gene therapy, as there is a possibility of using virus-like nanoparticles for targeted gene delivery. In addition, other biomedical applications that are explored using virus-like nanoparticles and the probable mechanism of delivering genes.

Matched MeSH terms: Capsid Proteins/chemistry*
Comparative genome analysis reveals a distinct influence of nucleotide composition on virus-host species-specific interaction of prawn-infecting nodavirus

Ismail SNFB, Baharum SN, Fazry S, Low CF

J Fish Dis, 2019 Dec;42(12):1761-1772.
PMID: 31637743 DOI: 10.1111/jfd.13093

Discovery of species-specific interaction between the host and virus has drawn the interest of many researchers to study the evolution of the newly emerged virus. Comparative genome analysis provides insights of the virus functional genome evolution and the underlying mechanisms of virus-host interactions. The analysis of nucleotide composition signified the evolution of nodavirus towards host specialization in a host-specific mutation manner. GC-rich genome of betanodavirus was significantly deficient in UpA and UpU dinucleotides composition, whilst the AU-rich genome of gammanodavirus was deficient in CpG dinucleotide. The capsid of MrNV and PvNV of gammanodavirus retains the highest abundance of adenine and uracil at the second codon position, respectively, which were found to be very distinctive from the other genera. ENC-GC3 plot inferred the influence of natural selection and mutational pressure in shaping the evolution of MrNV RdRp and capsid, respectively. Furthermore, CAI/eCAI analysis predicts a comparable adaptability of MrNV in squid, Sepia officinalis than its natural host, Macrobrachium rosenbergii. Thus, further study is warranted to investigate the capacity of MrNV replication in S. officinalis owing to its high codon adaptation index.

Matched MeSH terms: Capsid Proteins/genetics
A Potential MRI Agent and an Anticancer Drug Encapsulated within CPMV Virus-Like Particles

Aljabali AAA, Alzoubi L, Hamzat Y, Alqudah A, Obeid MA, Al Zoubi MS, et al.

Comb Chem High Throughput Screen, 2021;24(10):1557-1571.
PMID: 32928083 DOI: 10.2174/1386207323666200914110012

BACKGROUND: Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition.
OBJECTIVES: The plant virus Cowpea Mosaic Virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty Virus-Like Particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications.
METHODS: The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid.
RESULTS: Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis exhibited a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 μM and 3.9 μM, respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents.
CONCLUSION: Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines with its potency increased by 2.3-folds.

Matched MeSH terms: Capsid Proteins/chemistry*
Fulltext Rare rotavirus strains in children with severe diarrhea, Malaysia

Ch'ng LS, Lee WS, Kirkwood CD

Emerg Infect Dis, 2011 May;17(5):948-50.
PMID: 21529427 DOI: 10.3201/eid1705.101652
Matched MeSH terms: Capsid Proteins/genetics
Improved sensitivity of detection by avidin-biotin complex (ABC) immunocytochemistry in Epstein-Barr virus serology

Thoe SY, Sam CK, Cheng HM, Prasad U

J Med Virol, 1989 Dec;29(4):311-4.
PMID: 2559955

Serum antibodies against Epstein-Barr virus (EBV)-determined antigens have traditionally been titrated by the indirect immunofluorescence (IIF) technique. The avidin-biotin complex (ABC) immunocytochemical technique was used to determine the serum levels of IgA against EBV viral capsid antigen (IgA/VCA) and IgA against EBV early antigen (IgA/EA) in sera of 106 nasopharyngeal carcinoma (NPC) patients prior to treatment and 100 normal individuals. The sensitivity of the ABC technique is enhanced by an amplification of the antigen-antibody reaction, which involves the binding of the enzyme-linked ABC to the second biotinylated antibody. There was a good correlation (r = 0.9988) between ABC and IIF-determined IgA/VCA-positive titres, with the ABC technique being more sensitive than IIF in the detection of IgA/VCA in NPC sera: 94% (99/106) and 76% (80/106), respectively. The frequency of IgA/EA reactivity in NPC sera was also markedly increased by immunodetection with the ABC technique as compared with IIF technique: 63% (69/106) and 28% (30/106) respectively. Both the immunocytochemical techniques were equally specific in discriminating between elevated serum titres of IgA/VCA and IgA/EA in NPC sera from normal human sera.

Matched MeSH terms: Capsid Proteins*
Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice

Ch'ng WC, Saw WT, Yusoff K, Shafee N

Acta Virol., 2011;55(3):227-33.
PMID: 21978156

Enterovirus 71 (EV71) is one of the viruses that cause hand, foot and mouth disease. Its viral capsid protein 1 (VP1), which contains many neutralization epitopes, is an ideal target for vaccine development. Recently, we reported the induction of a strong immune response in rabbits to a truncated VP1 fragment (Nt-VP1t) displayed on a recombinant Newcastle disease virus (NDV) capsid protein. Protective efficacy of this vaccine, however, can only be tested in mice, since all EV71 animal models thus far were developed in mouse systems. In this study, we evaluated the type of immune responses against the protein developed by adult BALB/c mice. Nt-VP1t protein induced high levels of VP1 IgG antibody production in mice. Purified VP1 antigen stimulated activation, proliferation and differentiation of splenocytes harvested from these mice. They also produced significant levels of IFN-γ, a Th1-related cytokine. Taken together, Nt-VP1t protein is a potent immunogen in adult mice and our findings provide the data needed for testing of its protective efficacy in mouse models of EV71 infections.

Matched MeSH terms: Capsid Proteins/genetics; Capsid Proteins/immunology*
Development of a DNA vaccine against chicken anemia virus by using a bicistronic vector expressing VP1 and VP2 proteins of CAV

Moeini H, Omar AR, Rahim RA, Yusoff K

Comp Immunol Microbiol Infect Dis, 2011 May;34(3):227-36.
PMID: 21146874 DOI: 10.1016/j.cimid.2010.11.006

In the present study, we describe the development of a DNA vaccine against chicken anemia virus. The VP1 and VP2 genes of CAV were amplified and cloned into pBudCE4.1 to construct two DNA vaccines, namely, pBudVP1 and pBudVP2-VP1. In vitro and in vivo studies showed that co-expression of VP1 with VP2 are required to induce significant levels of antibody against CAV. Subsequently, the vaccines were tested in 2-week-old SPF chickens. Chickens immunized with the DNA-plasmid pBudVP2-VP1 showed positive neutralizing antibody titer against CAV. Furthermore, VP1-specific proliferation induction of splenocytes and also high serum levels of Th1 cytokines, IL-2 and IFN-γ were detected in the pBudVP2-VP1-vaccinated chickens. These results suggest that the recombinant DNA plasmid co-expressing VP1 and VP2 can be used as a potential DNA vaccine against CAV.

Matched MeSH terms: Capsid Proteins/genetics; Capsid Proteins/immunology*
Nanoglue: an alternative way to display cell-internalizing peptide at the spikes of hepatitis B virus core nanoparticles for cell-targeting delivery

Lee KW, Tey BT, Ho KL, Tejo BA, Tan WS

Mol Pharm, 2012 Sep 4;9(9):2415-23.
PMID: 22775561 DOI: 10.1021/mp200389t

Cell-internalizing peptides (CIPs) can be used to mediate specific delivery of nanoparticles across cellular membrane. The objective of this study was to develop a display technique using hepatitis B virus (HBV) capsid-binding peptide as a "nanoglue" to present CIPs on HBV nanoparticles for cell-targeting delivery. A CIP was selected from a phage display library and cross-linked specifically at the tips of the spikes of the HBV capsid nanoparticle via the "nanoglue" by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS). Fluorescent oligonucleotides packaged in the nanoparticles and the fluorescein molecules conjugated on the nanoparticles were delivered to cells by using this display technique. This study demonstrated a proof of principle for cell-targeting delivery via "nanoglue" bioconjugation.

Matched MeSH terms: Capsid Proteins/pharmacokinetics*; Capsid Proteins/chemistry

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