Identification and comparison of RCMV ALL 03 open reading frame (ORF) among several different strains of cytomegalovirus worldwide

Balakrishnan, Krishnan Nair; Abdullah, Ashwaq Ahmed; Bala, JamiluAbubakar; Abba, Yusuf; Sarah, Siti; Jesse, Faez Firdaus Abdullah; Nazariah, Zeenatul Allaudin; Noordin, M. M.; Lila, Mohd Azmi Mohd

doi:10.1016/j.meegid.2017.06.020

Cited by 9 publications

(4 citation statements)

References 58 publications

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“…Next, to elucidate the genomic features of ORFV strain UPM/HSN-20, a high-throughput DNA-sequencing approach was employed, a technique that proved to be efficient in revealing detailed genetic information of an organism. In addition to identifying pathogens faster, NGS technology and bioinformatics can provide new insights into the molecular mechanism of microbial pathogenesis ( Balakrishnan et al, 2017 ; Gwinn et al, 2019 ). Compared to Sanger sequencing, NGS technology has enabled researchers to study and understand the microbial world from broader and deeper perspectives.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis and Molecular Characterization of Orf Virus Strain UPM/HSN-20 Isolated From Goat in Malaysia

et al. 2022

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Contagious ecthyma commonly known as Orf is a globally important, highly contagious zoonotic, transboundary disease that affects domestic and wild ruminants. The disease is of great economic significance causing an immense impact on animal health, welfare, productivity, and trade. Detailed analysis of the viral genome is crucial to further elucidate the molecular mechanism of Orf virus (ORFV) pathogenesis. In the present study, a confluent monolayer of lamb testicle cells was infected with the processed scab sample obtained from an infected goat. The presence of the virus was confirmed using polymerase chain reaction and electron microscopy, while its genome was sequenced using next-generation sequencing technology. The genome sequence of Malaysian ORFV strain UPM/HSN-20 was found to contain 132,124 bp with a G + C content of 63.7%. The homology analysis indicates that UPM/HSN-20 has a high level of identity 97.3–99.0% with the other reference ORFV strain. Phylogenetic analysis revealed that ORFV strain UPM/HSN-20 is genetically more closely related to ORFV strain XY and NP from China. The availability of the genome-wide analysis of ORFV UPM/HSN-20 strain from Malaysia will serve as a good platform for further understanding of genetic diversity, ORFV infection, and strategic development for control measures.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis and Molecular Characterization of Orf Virus Strain UPM/HSN-20 Isolated From Goat in Malaysia

et al. 2022

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“…This results in the development of many animal models for the virus. 41 – 46 Seroprevalence studies have shown that 30–97% of the population is seropositive for CMV. 47 – 49 The immune system can easily control the virus from causing active infection and facilitating lifelong latency.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Cyclophilin A as a target in the treatment of cytomegalovirus infections

Abdullah

Nazariah

et al. 2018

Antivir Chem Chemother

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BackgroundViruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity.MethodsCytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins.ResultsIntermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug.ConclusionCyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

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“…Interestingly, this local strain (RCMV ALL-03) has been identified crossing the placenta infecting the pups making it suitable for congenital infection animal model (33). The availability of the complete genome sequence of this virus add on more advantages for pathogenicity study and antiviral development (34,35). Therefore, this study was conducted to screen combinations of siRNA for their cytotoxicity level and their effectiveness on inhibiting RCMV ALL-03 virus replication and gene expression.…”

Section: Introductionmentioning

confidence: 99%

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

Balakrishnan

Abdullah

Bala

et al. 2020

Preprint

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Background Cytomegalovirus (CMV) is an opportunistic pathogen that causes severe complications in congenitally infected newborns and non-immunocompetent individuals. Developing an effective vaccine is a major public health priority and current drugs are fronting resistance and side effects on recipients. In the present study, with the aim of exploring new strategies to counteract CMV replication, several anti-CMV siRNAs targeting IE2 and DNA polymerase gene regions were characterized and used as in combinations for antiviral therapy. Methods The rat embryo fibroblast (REF) cells were transfected with multi siRNA before infecting with CMV strain ALL-03. Viral growth inhibition was measured by TCID50, cytopathic effect (CPE) and droplet digital PCR (ddPCR) while IE2 and DNA polymerase gene knockdown was determined by real-time PCR. Ganciclovir was deployed as a control to benchmark the efficacy of antiviral activities of respective individual siRNAs. Results There was no cytotoxicity encountered for all the combinations of siRNAs on REF cells analyzed by MTT colorimetric assay (P > 0.05). Cytopathic effects (CPE) in cells infected by RCMV ALL-03 developed significantly less and at much slower rate compared to control group. The expression of targeted genes was downregulated successfully resulted in significant reduction (P < 0.05) of viral mRNA and DNA copies (dpb + dpc: 79%, 68%; dpb + ie2b: 68%, 60%; dpb + dpc + ie2b: 48%, 42%). Flow cytometry analysis showed a greater percentage of viable and early apoptosis of combined siRNAs-treated cells compared to control group. Notably, the siRNAs targeting gene regions were sequenced and no any mutation was identified, thereby avoiding the formation of mutant with potential resistant viruses. Conclusions In conclusion. The study demonstrated a tremendous promise of innovative approach with the deployment of combined siRNAs targeting at several genes simultaneously with the aim to control CMV replication in host cells.

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Identification and comparison of RCMV ALL 03 open reading frame (ORF) among several different strains of cytomegalovirus worldwide

Abstract: Genomic analysis of RCMV ALL-03 provided an overall picture of the whole genome organization and it served as a good platform for further understanding on the divergence in the family of Herpesviridae.

Cited by 9 publications

References 58 publications

Genome-Wide Analysis and Molecular Characterization of Orf Virus Strain UPM/HSN-20 Isolated From Goat in Malaysia

Genome-Wide Analysis and Molecular Characterization of Orf Virus Strain UPM/HSN-20 Isolated From Goat in Malaysia

Cyclophilin A as a target in the treatment of cytomegalovirus infections

Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03)

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