In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses

OBJECTIVE@#To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV).@*METHODS@#Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico.@*RESULTS@#One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity with all NiV and HeV G protein sequences, while the 15-mer M-epitope (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all NiV and HeV M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response.@*CONCLUSIONS@#Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against HeV and NiV. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.

In silico identification and characterization of common epitope-based peptide vaccine for Nipah and Hendra viruses

Objective To explore a common B- and T-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV). Methods Membrane proteins F, G and M of HeV and NiV were retrieved from the protein database and subjected to different bioinformatics tools to predict antigenic B-cell epitopes. Best B-cell epitopes were then analyzed to predict their T-cell antigenic potentiality. Antigenic B- and T-cell epitopes that shared maximum identity with HeV and NiV were selected. Stability of the selected epitopes was predicted. Finally, the selected epitopes were subjected to molecular docking simulation with HLA-DR to confirm their antigenic potentiality in silico. Results One epitope from G proteins, one from M proteins and none from F proteins were selected based on their antigenic potentiality. The epitope from the G proteins was stable whereas that from M was unstable. The M-epitope was made stable by adding flanking dipeptides. The 15-mer G-epitope (VDPLRVQWRNNSVIS) showed at least 66% identity with all NiV and HeV G protein sequences, while the 15-mer M-epitope (GKLEFRRNNAIAFKG) with the dipeptide flanking residues showed 73% identity with all NiV and HeV M protein sequences available in the database. Molecular docking simulation with most frequent MHC class-II (MHC II) and class-I (MHC I) molecules showed that these epitopes could bind within HLA binding grooves to elicit an immune response. Conclusions Data in our present study revealed the notion that the epitopes from G and M proteins might be the target for peptide-based subunit vaccine design against HeV and NiV. However, the biochemical analysis is necessary to experimentally validate the interaction of epitopes individually with the MHC molecules through elucidation of immunity induction.

Nipah Encephalitis – An Update

Between September 1998 to May 1999, Malaysia and Singapore were hit by an outbreak of fatal encephalitis caused by a novel virus from the paramyxovirus family. This virus was subsequently named as Nipah virus, after the Sungei Nipah village in Negeri Sembilan, where the virus was first isolated. The means of transmission was thought to be from bats-topigs and subsequently pigs-to-human. Since 2001, almost yearly outbreak of Nipah encephalitis has been reported from Bangladesh and West Bengal, India. These outbreaks were characterized by direct bats-to-human, and human-to-human spread of infection. Nipah virus shares many similar characteristics to Hendra virus, first isolated in an outbreak of respiratory illness involving horses in Australia in 1994. Because of their homology, a new genus called Henipavirus (Hendra + Nipah) was introduced. Henipavirus infection is a human disease manifesting most often as acute encephalitis (which may be relapsing or late-onset) or pneumonia, with a high mortality rate. Pteropus bats act as reservoir for the virus, which subsequently lead to human spread. Transmission may be from consumption of food contaminated by bats secretion, contact with infected animals, or human-to-human spread. With wide geographical distribution of Pteropus bats, Henipavirus infection has become an important emerging human infection with worldwide implication.

The Mechanism of Henipavirus Fusion: Examining the Relationships between the Attachment and Fusion Glycoproteins / 中国病毒学·英文版

The henipaviruses, represented by Nipah virus and Hendra virus, are emerging zoonotic viral pathogens responsible for repeated outbreaks associated with high morbidity and mortality in Australia, Southeast Asia, India and Bangladesh. These viruses enter host cells via a class I viral fusion mechanism mediated by their attachment and fusion envelope glycoproteins; efficient membrane fusion requires both these glycoproteins in conjunction with specific virus receptors present on susceptible host cells. The henipavirus attachment glycoprotein interacts with a cellular B class ephrin protein receptor triggering conformational alterations leading to the activation of the viral fusion (F) glycoprotein. The analysis of monoclonal antibody (mAb) reactivity with G has revealed measurable alterations in the antigenic structure of the glycoprotein following its binding interaction with receptor. These observations only appear to occur with full-length native G glycoprotein, which is a tetrameric oligomer, and not with soluble forms of G (sG), which are disulfide-linked dimers. Single amino acid mutations in a heptad repeat-like structure within the stalk domain of G can disrupt its association with F and subsequent membrane fusion promotion activity. Notably, these mutants of G also appear to confer a postreceptor bound conformation implicating the stalk domain as an important element in the G glycoprotein's structure and functional relationship with F. Together, these observations suggest fusion is dependent on a specific interaction between the F and G glycoproteins of the henipaviruses. Further, receptor binding induces measurable changes in the G glycoprotein that appear to be greatest in respect to the interactions between the pairs of dimers comprising its native tetrameric structure. These receptor-induced conformational changes may be associated with the G glycoprotein's promotion of the fusion activity of F.

Hendra Virus Re-visited / 中国病毒学·英文版

Hendra virus, a novel member of the family Paramyxovirus that has emerged from bats in Australia, causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994, resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses; there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors (plausibly be environmental, biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes, of virus infection dynamics in flying foxes, and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses, and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus, of the proximate factors associated with spillover, and the inherent difficulties of effectively managing wild populations, preclude a management approach targeted at bats.

Epidemiological surveillance of Henipavirus in Chongqing / 中华微生物学和免疫学杂志

Objective To establish nucleic acid testing techniques for detecting Nipah virus (NiV) and Hendra virus (HeV), and to test the NiV and HeV in peripheral blood collected from domestic pigs, cows and goats in Chongqing. Methods Peripheral blood samples of 580 domestic pigs, 250 cows, 180 goats were collected from Chongqing since June 2007 to June 2008. The lymphocytes were separated by density gradient centrifugation and total RNA was extracted using Trizol method for detection of NiV and HeV with one-step real-time RT-PCR. Sequence identification and analysis were performed for positive PCR prod-ucts. Virus isolation and culture were adopted for positive samples, and epidemiologic reports were submit-ted. Results Nucleic acid detections searching for NiV and HeV were successfully performed in animal blood samples collected from Chongqing. "Takeoff points" were not found in fluorescence amplification curves of all samples. Curves kept the same slope, and assays were judged as negative. Conclusion Until now, Neither NiV or HeV infection has been found in domestic animals blood samples collected from Chongqing, which suggest a lower possibility of outbreaks of Nipah disease and Hendra disease in Chongqing in the near future.