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BARF1 gene silencing triggers caspase-dependent mitochondrial apoptosis in Epstein-Barr virus-positive malignant cells

Mohidin TB, Ng CC

J Biosci, 2015 Mar;40(1):41-51.
PMID: 25740140

Epstein-Barr virus (EBV)-encoded BARF1 (BamH1-A Rightward Frame-1) is expressed in EBV-positive malignancies such as nasopharyngeal carcinoma, EBV-associated gastric cancer, B-cell lymphoma and nasal NK/T-cell lymphoma, and has been shown to have an important role in oncogenesis. However, the mechanism by which BARF1 elicits its biological effects is unclear. We investigated the effects of BARF1 silencing on cell proliferation and apoptosis in EBV-positive malignant cells. We observed that BARF1 silencing significantly inhibits cell proliferation and induces apoptosis-mediated cell death by collapsing the mitochondrial membrane potential in AG876 and Hone-Akata cells. BARF1 knockdown up-regulates the expression of pro-apoptotic proteins and downregulates the expression of anti-apoptotic proteins. In BARF1-down-regulated cells, the Bcl-2/BAX ratio is decreased. The caspase inhibitor z-VAD-fmk was found to rescue siBARF1-induced apoptosis in these cells. Immunoblot analysis showed significant increased levels of cleaved caspase 3 and caspase 9. We observed a significant increase in cytochrome c level as well as the formation of apoptosome complex in BARF1-silenced cells. In conclusion, siRNA-mediated BARF1 down-regulation induces caspase-dependent apoptosis via the mitochondrial pathway through modulation of Bcl-2/BAX ratio in AG876 and Hone-Akata cells. Targeting BARF1 using siRNA has the potential to be developed as a novel therapeutic strategy in the treatment of EBV-associated malignancies.

Matched MeSH terms: Viral Proteins/genetics*
Fulltext Improving the potency of DNA vaccine against chicken anemia virus (CAV) by fusing VP1 protein of CAV to Marek's Disease Virus (MDV) type-1 VP22 protein

Moeini H, Omar AR, Rahim RA, Yusoff K

Virol J, 2011;8:119.
PMID: 21401953 DOI: 10.1186/1743-422X-8-119

Studies have shown that the VP22 gene of Marek's Disease Virus type-1 (MDV-1) has the property of movement between cells from the original cell of expression into the neighboring cells. The ability to facilitate the spreading of the linked proteins was used to improve the potency of the constructed DNA vaccines against chicken anemia virus (CAV).

Matched MeSH terms: Viral Proteins/genetics
Epstein-Barr virus DNA detection in the diagnosis of nasopharyngeal carcinoma

Yap YY, Hassan S, Chan M, Choo PK, Ravichandran M

Otolaryngol Head Neck Surg, 2007 Jun;136(6):986-91.
PMID: 17547993

OBJECTIVES: This study examines the presence of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) by using polymerase chain reaction (PCR).
STUDY DESIGN: Eighty-six postnasal biopsy samples and 71 fine-needle aspirate samples of neck masses were obtained from patients who were clinically suspect for NPC. Genomic DNA was extracted from the samples, and EBNA1, EBNA2, and LMP genes of EBV were detected by PCR. PCR results were compared with NPC histopathology findings.
RESULTS: The sensitivity of PCR to detect EBNA1 (97.14%), EBNA2 (88.57%), and LMP (91.43%) genes of EBV in nasopharyngeal biopsy samples were higher than those in fine-needle aspirate samples.
CONCLUSION: Detection of EBV by PCR in tissue obtained from nasopharyngeal biopsy and fine-needle aspirate samples of neck masses is a relatively inexpensive, reliable, and accurate method of diagnosing NPC. Detection of EBV genes is on par with histopathological examination (HPE) and superior to fine-needle aspirate cytology.
SIGNIFICANCE: PCR is an ideal tool for suggesting NPC and guiding the diagnostic workup in occult primary tumors, facilitating earlier diagnosis and reducing morbidity and mortality.

Matched MeSH terms: Viral Proteins/genetics
Expression and purification of a recombinant scFv towards the exotoxin of the pathogen, Burkholderia pseudomallei

Lim KP, Li H, Nathan S

J Microbiol, 2004 Jun;42(2):126-32.
PMID: 15357306

A single chain variable fragment (scFv) specific towards B. pseudomallei exotoxin had previously been generated from an existing hybridoma cell line (6E6AF83B) and cloned into the phage display vector pComb3H. In this study, the scFv was subcloned into the pComb3X vector to facilitate the detection and purification of expressed antibodies. Detection was facilitated by the presence of a hemagglutinin (HA) tag, and purification was facilitated by the presence of a histidine tag. The culture was grown at 30 degrees C until log phase was achieved and then induced with 1 mM IPTG in the absence of any additional carbon source. Induction was continued at 30 degrees C for five h. The scFv was discerned by dual processes-direct enzyme-linked immunosorbent assays (ELISA), and Western blotting. When compared to E. coli strains ER2537 and HB2151, scFv expression was observed to be highest in the E. coli strain Top10F'. The expressed scFv protein was purified via nickel-mediated affinity chromatography and results indicated that two proteins a 52 kDa protein, and a 30 kDa protein were co-purified. These antibodies, when blotted against immobilized exotoxin, exhibited significant specificity towards the exotoxin, compared to other B. pseudomallei antigens. Thus, these antibodies should serve as suitable reagents for future affinity purification of the exotoxin.

Matched MeSH terms: Viral Proteins/genetics
Chimeric Newcastle disease virus nucleocapsid with parts of viral hemagglutinin-neuraminidase and fusion proteins

Rabu A, Tan WS, Kho CL, Omar AR, Yusoff K

Acta Virol., 2002;46(4):211-7.
PMID: 12693857

The nucleocapsid (NP) protein of Newcastle disease virus (NDV) self-assembled in Escherichia coli as ring-like and herringbone-like particles. Several chimeric NP proteins were constructed in which the antigenic regions of the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of NDV, myc epitope, and six histidines (a hexa-His tag) were linked to the C-terminus of the NP monomer. These chimeric proteins were expressed efficiently in soluble form in E. coli as detected by Western blot analysis. Electron microscopy of the purified products revealed that they self-assembled into ring-like particles. These chimeric particles exhibited antigenicity of the myc epitope, suggesting that the foreign sequences were exposed on the surface of the particles. Chickens inoculated with the chimeric particles mounted an immune response against NDV, suggesting the possibility of use of the ring-like particle as a carrier of immunogens in subunit vaccines and immunological reagents.

Matched MeSH terms: Viral Proteins/genetics
Fulltext Nipah virus: a recently emergent deadly paramyxovirus

Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK, et al.

Science, 2000 May 26;288(5470):1432-5.
PMID: 10827955

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Matched MeSH terms: Viral Proteins/genetics
Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia

Chua KB, Wang LF, Lam SK, Crameri G, Yu M, Wise T, et al.

Virology, 2001 May 10;283(2):215-29.
PMID: 11336547

A search for the natural host of Nipah virus has led to the isolation of a previously unknown member of the family Paramyxoviridae. Tioman virus (TiV) was isolated from the urine of fruit bats (Pteropus hypomelanus) found on the island of the same name off the eastern coast of peninsular Malaysia. An electron microscopic study of TiV-infected cells revealed spherical and pleomorphic-enveloped viral particles (100--500 nm in size) with a single fringe of embedded peplomers. Virus morphogenesis occurred at the plasma membrane of infected cells and morphological features of negative-stained ribonucleoprotein complexes were compatible with that of viruses in the family Paramyxoviridae. Serological studies revealed no cross-reactivity with antibodies against a number of known Paramyxoviridae members except for the newly described Menangle virus (MenV), isolated in Australia in 1997. Failure of PCR amplification using MenV-specific primers suggested that this new virus is related to but different from MenV. For molecular characterization of the virus, a cDNA subtraction strategy was employed to isolate virus-specific cDNA from virus-infected cells. Complete gene sequences for the nucleocapsid protein (N) and phosphoprotein (P/V) have been determined and recombinant N and V proteins produced in baculovirus. The recombinant N and V proteins reacted with porcine anti-MenV sera in Western blot, confirming the serological cross-reactivity observed during initial virus characterization. The lack of a C protein-coding region in the P/V gene, the creation of P mRNA by insertion of 2-G residues, and the results of phylogenetic analyses all indicated that TiV is a novel member of the genus Rubulavirus.

Matched MeSH terms: Viral Proteins/genetics
Detection of human herpesvirus 7 in salivary glands

Yadav M, Nambiar S, Khoo SP, Yaacob HB

Arch Oral Biol, 1997 Aug;42(8):559-67.
PMID: 9347118

The prevalence and cellular distribution of human herpesvirus 7 (HHV-7) in archival labial salivary glands was analysed for virus-specific DNA sequences by polymerase chain reaction (PCR) and in situ hybridization signals. In addition, the cellular expression of HHV-7-encoded protein was detected by immunohistochemical staining with a virus-specific monoclonal antibody. Eleven of 20 samples were positive for the HHV-7 DNA sequence by PCR. Eighteen of 20 tissues analysed by in situ hybridization showed signals in ductal, serous and mucous cells. Some nuclei of these cells and also the myoepithelial population were positive. In immunolocalization studies, all 20 salivary glands consistently showed HHV-7-expressed protein in the cytoplasm of ductal cuboidal and columnar cells. The protein was also found in the cytoplasm of mucous and serous acinar cells that were immunopositive for HHV-7. The observations are consistent with the suggestion that the labial salivary gland is a site for virus replication, potential persistence and a source of infective HHV-7 in saliva.

Matched MeSH terms: Viral Proteins/genetics
A review of Nipah and Hendra viruses with an historical aside

Ksiazek TG, Rota PA, Rollin PE

Virus Res, 2011 Dec;162(1-2):173-83.
PMID: 21963678 DOI: 10.1016/j.virusres.2011.09.026

The emergence of Hendra and Nipah viruses in the 1990s has been followed by the further emergence of these viruses in the tropical Old World. The history and current knowledge of the disease, the viruses and their epidemiology is reviewed in this article. A historical aside summarizes the role that Dr. Brian W.J. Mahy played at critical junctures in the early stories of these viruses.

Matched MeSH terms: Viral Proteins/genetics
Fulltext Indirect ELISA based on Hendra and Nipah virus proteins for the detection of henipavirus specific antibodies in pigs

Fischer K, Diederich S, Smith G, Reiche S, Pinho Dos Reis V, Stroh E, et al.

PLoS One, 2018;13(4):e0194385.
PMID: 29708971 DOI: 10.1371/journal.pone.0194385

Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus in the family Paramyxoviridae. Henipavirus infections were first reported in the 1990's causing severe and often fatal outbreaks in domestic animals and humans in Southeast Asia and Australia. NiV infections were observed in humans in Bangladesh, India and in the first outbreak in Malaysia, where pigs were also infected. HeV infections occurred in horses in the North-Eastern regions of Australia, with singular transmission events to humans. Bats of the genus Pteropus have been identified as the reservoir hosts for henipaviruses. Molecular and serological indications for the presence of henipa-like viruses in African fruit bats, pigs and humans have been published recently. In our study, truncated forms of HeV and NiV attachment (G) proteins as well as the full-length NiV nucleocapsid (N) protein were expressed using different expression systems. Based on these recombinant proteins, Enzyme-linked Immunosorbent Assays (ELISA) were developed for the detection of HeV or NiV specific antibodies in porcine serum samples. We used the NiV N ELISA for initial serum screening considering the general reactivity against henipaviruses. The G protein based ELISAs enabled the differentiation between HeV and NiV infections, since as expected, the sera displayed higher reactivity with the respective homologous antigens. In the future, these assays will present valuable tools for serosurveillance of swine and possibly other livestock or wildlife species in affected areas. Such studies will help assessing the potential risk for human and animal health worldwide by elucidating the distribution of henipaviruses.

Matched MeSH terms: Viral Proteins/genetics
Immune responses in mice and pigs after oral vaccination with rabies virus vectored Nipah disease vaccines

Shuai L, Ge J, Wen Z, Wang J, Wang X, Bu Z

Vet Microbiol, 2020 Feb;241:108549.
PMID: 31928698 DOI: 10.1016/j.vetmic.2019.108549

Nipah virus (NiV) is a re-emerging zoonotic pathogen that causes high mortality in humans and pigs. Oral immunization in free-roaming animals is one of the most practical approaches to prevent NiV pandemics. We previously generated a recombinant rabies viruses (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain, rERAG333E, which contains a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) and serves as an oral vaccine for dog rabies. In this study, we generated two recombinant RABVs, rERAG333E/NiVG and rERAG333E/NiVF, expressing the NiV Malaysian strain attachment glycoprotein (NiV-G) or fusion glycoprotein (NiV-F) gene based on the rERAG333E vector platform. Both rERAG333E/NiVG and rERAG333E/NiVF displayed growth properties similar to those of rERAG333E and caused marked syncytia formation after co-infection in BSR cell culture. Adult and suckling mice intracerebrally inoculated with the recombinant RABVs showed NiV-G and NiV-F expression did not increase the virulence of rERAG333E. Oral vaccination with rERAG333E/NiVG either singularly or combined with rERAG333E/NiVF induced significant NiV neutralizing antibody against NiV and RABV, and IgG to NiV-G or NiV-F in mice and pigs. rERAG333E/NiVG and rERAG333E/NiVF thus appeared to be suitable candidates for further oral vaccines for potential animal targets in endemic areas of NiV disease and rabies.

Matched MeSH terms: Viral Proteins/genetics
Fulltext Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside

Ayipo YO, Yahaya SN, Alananzeh WA, Babamale HF, Mordi MN

Infect Genet Evol, 2021 Sep;93:104944.
PMID: 34052418 DOI: 10.1016/j.meegid.2021.104944

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-β and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.

Matched MeSH terms: Viral Proteins/genetics
Fulltext Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease

Mire CE, Versteeg KM, Cross RW, Agans KN, Fenton KA, Whitt MA, et al.

Virol J, 2013 Dec 13;10:353.
PMID: 24330654 DOI: 10.1186/1743-422X-10-353

BACKGROUND: Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection.
METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.
CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.

Matched MeSH terms: Viral Proteins/genetics
Design and validation of small interfering RNA on respiratory syncytial virus M2-2 gene: A potential approach in RNA interference on viral replication

Chin VK, Atika Aziz NA, Hudu SA, Harmal NS, Syahrilnizam A, Jalilian FA, et al.

J Virol Methods, 2016 10;236:117-125.
PMID: 27432115 DOI: 10.1016/j.jviromet.2016.07.012

Human respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants and young children globally and is a significant pathogen of the elderly and immunocompromised. The M2-2 protein of respiratory syncytial virus (RSV) is particularly important in regulation of viral RNA transcription and replication that could be a potential anti-viral candidate against RSV infection. In this study, we designed and validated siRNAs that specifically target the RSV M2-2 gene. Four siRNAs targeting different regions of the M2-2 gene were designed using web tool. In-vitro evaluation of silencing effect was performed by using RSV infected Vero cell line. Viral M2-2 linked GFP recombinant plasmid was co-transfected with non-targeted siRNA, Pooled siRNA, siRNA 1, siRNA 2, siRNA 3 and siRNA 4 using synthetic cationic polymer. The silencing effect of M2-2 gene at the protein level was measured both qualitatively and quantitatively by using fluorescence microscopy and flow cytometry. Meanwhile, the silencing effect at the mRNA level was assessed by using RT-qPCR. This study showed that all four designed siRNAs can effectively and efficiently silence M2-2 gene. siRNA 2 showed the highest (98%) silencing effect on protein level and siRNA 4 with 83.1% at the mRNA level. The viral assay showed no significant cytopathic effects observed after 6days post-infection with siRNAs. In conclusion, this study showed the effectiveness of siRNA in silencing M2-2 gene both at the protein and mRNA level which could potentially be used as a novel therapeutic agent in the treatment of RSV infection. However, further study is warranted to investigate the silencing effect of M2-2 protein and inhibition of RSV infection.

Matched MeSH terms: Viral Proteins/genetics*
Recombineering linear BACs

Chen Q, Narayanan K

Methods Mol Biol, 2015;1227:27-54.
PMID: 25239740 DOI: 10.1007/978-1-4939-1652-8_2

Recombineering is a powerful genetic engineering technique based on homologous recombination that can be used to accurately modify DNA independent of its sequence or size. One novel application of recombineering is the assembly of linear BACs in E. coli that can replicate autonomously as linear plasmids. A circular BAC is inserted with a short telomeric sequence from phage N15, which is subsequently cut and rejoined by the phage protelomerase enzyme to generate a linear BAC with terminal hairpin telomeres. Telomere-capped linear BACs are protected against exonuclease attack both in vitro and in vivo in E. coli cells and can replicate stably. Here we describe step-by-step protocols to linearize any BAC clone by recombineering, including inserting and screening for presence of the N15 telomeric sequence, linearizing BACs in vivo in E. coli, extracting linear BACs, and verifying the presence of hairpin telomere structures. Linear BACs may be useful for functional expression of genomic loci in cells, maintenance of linear viral genomes in their natural conformation, and for constructing innovative artificial chromosome structures for applications in mammalian and plant cells.

Matched MeSH terms: Viral Proteins/genetics*
Fulltext Analysis of anoxybacillus genomes from the aspects of lifestyle adaptations, prophage diversity, and carbohydrate metabolism

Goh KM, Gan HM, Chan KG, Chan GF, Shahar S, Chong CS, et al.

PLoS One, 2014;9(6):e90549.
PMID: 24603481 DOI: 10.1371/journal.pone.0090549

Species of Anoxybacillus are widespread in geothermal springs, manure, and milk-processing plants. The genus is composed of 22 species and two subspecies, but the relationship between its lifestyle and genome is little understood. In this study, two high-quality draft genomes were generated from Anoxybacillus spp. SK3-4 and DT3-1, isolated from Malaysian hot springs. De novo assembly and annotation were performed, followed by comparative genome analysis with the complete genome of Anoxybacillus flavithermus WK1 and two additional draft genomes, of A. flavithermus TNO-09.006 and A. kamchatkensis G10. The genomes of Anoxybacillus spp. are among the smaller of the family Bacillaceae. Despite having smaller genomes, their essential genes related to lifestyle adaptations at elevated temperature, extreme pH, and protection against ultraviolet are complete. Due to the presence of various competence proteins, Anoxybacillus spp. SK3-4 and DT3-1 are able to take up foreign DNA fragments, and some of these transferred genes are important for the survival of the cells. The analysis of intact putative prophage genomes shows that they are highly diversified. Based on the genome analysis using SEED, many of the annotated sequences are involved in carbohydrate metabolism. The presence of glycosyl hydrolases among the Anoxybacillus spp. was compared, and the potential applications of these unexplored enzymes are suggested here. This is the first study that compares Anoxybacillus genomes from the aspect of lifestyle adaptations, the capacity for horizontal gene transfer, and carbohydrate metabolism.

Matched MeSH terms: Viral Proteins/genetics
Fulltext Dissecting the dynamics of HIV-1 protein sequence diversity

Hu Y, Tan PT, Tan TW, August JT, Khan AM

PLoS One, 2013;8(4):e59994.
PMID: 23593157 DOI: 10.1371/journal.pone.0059994

The rapid mutation of human immunodeficiency virus-type 1 (HIV-1) and the limited characterization of the composition and incidence of the variant population are major obstacles to the development of an effective HIV-1 vaccine. This issue was addressed by a comprehensive analysis of over 58,000 clade B HIV-1 protein sequences reported over at least 26 years. The sequences were aligned and the 2,874 overlapping nonamer amino acid positions of the viral proteome, each a possible core binding domain for human leukocyte antigen molecules and T-cell receptors, were quantitatively analyzed for four patterns of sequence motifs: (1) "index", the most prevalent sequence; (2) "major" variant, the most common variant sequence; (3) "minor" variants, multiple different sequences, each with an incidence less than that of the major variant; and (4) "unique" variants, each observed only once in the alignment. The collective incidence of the major, minor, and unique variants at each nonamer position represented the total variant population for the position. Positions with more than 50% total variants contained correspondingly reduced incidences of index and major variant sequences and increased minor and unique variants. Highly diverse positions, with 80 to 98% variant nonamer sequences, were present in each protein, including 5% of Gag, and 27% of Env and Nef, each. The multitude of different variant nonamer sequences (i.e. nonatypes; up to 68%) at the highly diverse positions, represented by the major, multiple minor, and multiple unique variants likely supported variants function both in immune escape and as altered peptide ligands with deleterious T-cell responses. The patterns of mutational change were consistent with the sequences of individual HXB2 and C1P viruses and can be considered applicable to all HIV-1 viruses. This characterization of HIV-1 protein mutation provides a foundation for the design of peptide-based vaccines and therapeutics.

Matched MeSH terms: Viral Proteins/genetics*
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: Viral Proteins/genetics
Fulltext Monitoring of the h275y mutation in pandemic influenza A(H1N1) 2009 strains isolated in Malaysia

Suppiah J, Yusof MA, Othman KA, Saraswathy TS, Thayan R, Kasim FM, et al.

Southeast Asian J. Trop. Med. Public Health, 2011 Jan;42(1):100-4.
PMID: 21323171

The 2009 pandemic influenza A(H1N1) infection in Malaysia was first reported in May 2009 and oseltamivir was advocated for confirmed cases in postexposure prophylaxis. However, there are cases of oseltamivir-resistance reported among H1N1-positive patients in other countries. Resistance is due to substitution of histidine by tyrosine at residue 275 (H275Y) of neuraminidase (NA). In this study, we have employed Sanger sequencing method to investigate the occurrence of mutations in NA segments of 67 pandemic 2009 A(H1N1) viral isolates from Malaysian patients that could lead to probable oseltamivir resistance. The sequencing analysis did not yield mutation at residue 275 for all 67 isolates indicating that our viral isolates belong to the wild type and do not confer resistance to oseltamivir.

Matched MeSH terms: Viral Proteins/genetics
Genetic diversity of Chinese rabies viruses: evidence for the presence of two distinct clades in China

Zhang YZ, Xiong CL, Lin XD, Zhou DJ, Jiang RJ, Xiao QY, et al.

Infect Genet Evol, 2009 Jan;9(1):87-96.
PMID: 19041424 DOI: 10.1016/j.meegid.2008.10.014

There have been three major rabies epidemics in China since the 1950s. To gain more insights into the molecular epidemiology of rabies viruses (RVs) for the third (the current) epidemic, we isolated RV from dogs and humans in major endemic areas, and characterized these isolates genetically by sequencing the entire glycoprotein (G) gene and the G-L non-coding region. These sequences were also compared phylogenetically with RVs isolated in China during previous epidemics and those around the world. Comparison of the entire G genes among the Chinese isolates revealed up to 21.8% divergence at the nucleotide level and 17.8% at the amino acid level. The available Chinese isolates could be divided into two distinct clades, each of which could be further divided into six lineages. Viruses in clade I include most of the Chinese viruses as well as viruses from southeast Asian countries including Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. The viruses in the other clade were found infrequently in China, but are closely related to viruses distributed worldwide among terrestrial animals. Interestingly, most of the viruses isolated during the past 10 years belong to lineage A viruses within clade I whereas most of the viruses isolated before 1996 belong to other lineages within clades I and II. Our results indicated that lineages A viruses have been predominant during the past 10 years and thus are largely responsible for the third and the current epidemic in China. Our results also suggested that the Chinese RV isolates in clade I share a common recent ancestor with those circulating in southeast Asia.

Matched MeSH terms: Viral Proteins/genetics

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