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UK Health Security Agency

NCPV in research 2018

NCPV is primarily comprised of viruses that require handling at biosafety levels 2, 3 and 4. In this article, 5 scientific papers that were published in 2018 and which used NCPV strains are highlighted.

Japanese Encephalitis Virus

One of the most important causes of viral encephalitis in humans is Japanese encephalitis virus (JEV). JEV is a positive single-stranded RNA virus belonging to the family Flaviviridae that causes an estimated 68,000 cases of viral encephalitis each year and has a mortality rate of 14% to 21% 1. Up to 50% of those that survive the infection suffer with long term neurological sequelae and JEV is therefore considered to be of high clinical importance 1. NCPV provided Nakayama strain of JEV to García-Nicolás et al., (2018) which was used in their research on JEV transmission in pigs ‘Targeting of the Nasal Mucosa by Japanese Encephalitis Virus for Non-Vector-Borne Transmission’. JEV has complex ecology consisting of two separate life cycles, including an amplification cycle in pigs, followed by transmission to mosquitos, then humans1. Their research indicates that the port of entry and exit of JEV in direct transmission between pigs is the epithelium of the upper respiratory tract1. This research has provided a greater understanding of the mechanism of direct transmission of JEV in pigs which potentially may also be relevant to other flaviviruses.

Respiratory Syncytial Virus

Recent research has also been conducted using NCPV’s Respiratory Syncytial Virus (RSV) A2 strain by Brookes et al., (2018). RSV belongs to the family Paramyxoviridae and is the most common cause of lower respiratory tract acute infections in children2. RSV replication primarily occurs within the cytoplasm of epithelial cells which comprise the pseudostratified layer of the bronchial airway. All attempts to provide an effective therapy for RSV so far have been unsuccessful2. Brookes et al., (2018) added compounds such as GS-5806 and PC786 to the RSV A2 obtained from NCPV in order to test their anti-viral capabilities. Their results showed that GS-5806 and PC786 had contrasting effects. GS-5806 did not show any significant anti-viral effects on RSV A2. PC786 resulted in increased levels of CCL5, IL-6, double-strand DNA and mucin and inhibition of RSV A2 was observed2. PC786 therefore could potentially be used as a therapeutic agent to treat active RSV infections.

Chikungunya Virus

Chikungunya virus (CHIKV), an enveloped positive-sense, single-stranded RNA alphavirus, was first documented more than 6 decades ago. While only one serotype of CHIKV exists, it is classified into three genotypes based on geographical location3. In 2005, there were reports of a large outbreak of CHIKV on the islands of the Indian Ocean which affected one third of their population and caused more than 200 mortalities3. In response to the spread of CHIKV, Tuekprakhon et al., (2018) produced and characterised panels of antibodies against CHIKV structural proteins. These new antibodies were tested for their cross reactivity with other viruses including the following alphaviruses O’nyong’nyong virus (ONNV, strain Ahero), Mayaro virus (MAYV, strain TC652), Ross River virus (RRV), Venezuelan Equine Encephalitis virus (VEEV, strains 78v and TrD), Eastern Equine Encephalitis virus (EEEV, strain H178/99), Sindbis Virus (SINV, strain EGAR339), and Western Equine Encephalitic virus (WEEV, strain H160/99) that were acquired from NCPV3. With the use of these authenticated viruses obtained from NCPV, Tuekprakhon et al., (2008) were able to improve clinical diagnosis and surveillance of CHIKV infections.

Human Herpesvirus

One of the most prevalent viruses within the human population is Human Herpes Virus 6 (HHV-6). HHV-6, like other herpesviruses, establishes lifelong infection in humans. It is prevalent in healthy humans but in immunosuppressed carriers it can result in a variety of diseases later in life; such as multiple sclerosis4. HHV-6 contains two virus species known as HHV-6A and HHV-6B. Treatment of HHV-6 infection usually involves drugs which have significant side effects such as kidney failure and bone marrow depression4. Research from Martin et al., (2018) used the HHV-6A U1102 strain and the HHV-6B HST strain provided by NCPV to analyse the CD8 T cell immunity to HHV-6B. The research describes 16 new structures that CD8 T cells can utilise in order to recognise and kill HHV-6B-infected cells4. These results aid the advancements of immunotherapies such as adoptive T cell therapy as well as help to progress the development of vaccines against HHV-6.

Dengue and Chikungunya Viruses

The use of metagenomic sequencing could potentially result in unbiased identification of pathogens from clinical samples alongside diagnostics of infectious diseases5. In addition to this, the data could provide information relevant for treatment, prognosis as well as detecting and tracking outbreaks of infectious diseases5. MinION, a single-molecule genome sequencer developed by Oxford Nanopore Technologies, is an example of a metagenomic sequencer that could be used to identify different viruses without the need for prior culture and target enrichment. However, when sequencing directly from samples with a potential wide range of viral titres, users must be conscious of potential cross contamination5. Xu et al., (2018) assessed the extent and source of cross contamination by generating a unique sequencing dataset of influenza A virus (obtained from a ferret nasal wash) Chikungunya virus strain S27 and Dengue virus strain TC861HA (obtained from NCPV). These samples were prepared separately and sequenced in individual flow cells, and also pooled for multiplex sequencing5. Within the multiplex sequencing data 0.056% of total reads were assigned to the wrong barcode, predominantly as a result of chimeric reads5. This highlights the necessity of carefully filtering data when executing multiple sequences before performing downstream analysis5.

If the use of our viruses results in a scientific publication, it should be cited in the publication as: ‘Virus Name’ (NCPV ‘Catalogue Number’). If the use of an NCPV virus results in a scientific publication we would like to hear from you and you could be featured in our newsletter or on the Culture Collections' website: contact us

Culture Collections specialise in preserving and distributing viral strains. We offer secure, confidential, second site storage facilities and patent depositing services for your valuable viral stocks and also offer a catalogue deposit service where your deposited organisms will be maintained by experienced staff and included in our online catalogue. Please see all of our latest assessions to our NCPV catalogue here.

References

  1. García-Nicolás, O., Braun, R., Milona, P., Lewandowska, M., Dijkman, R., Alves, M. and Summerfield, A. 2018. Targeting of the Nasal Mucosa by Japanese Encephalitis Virus for Non-Vector-Borne Transmission. Journal of Virology, 92(24). DOI: 10.1128/JVI.01091-18

  2.  Brookes, D., Coates, M., Allen, H., Daly, L., Constant, S., Huang, S., Hows, M., Davis, A., Cass, L., Ayrton, J., Knowles, I., Strong, P., Rapeport, G. and Ito, K. 2018. Late therapeutic intervention with a respiratory syncytial virus L-protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium. British Journal of Pharmacology, 175(12), 2520-2534. DOI: 10.1111/bph.14221

  3. Tuekprakhon, A., Puiprom, O., Sasaki, T., Michiels, J., Bartholomeeusen, K., Nakayama, E., Meno, M., Phadungsombat, J., Huits, R., Ariën, K., Luplertlop, N., Shioda, T. and Leaungwutiwong, P. 2018. Broad-spectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development. PLOS ONE, 13(12), e0208851. DOI: 10.1371/journal.pone.0208851

  4. Martin, L., Hollaus, A., Stahuber, A., Hübener, C., Fraccaroli, A., Tischer, J., Schub, A. and Moosmann, A. 2018. Cross-sectional analysis of CD8 T cell immunity to human herpesvirus 6B. PLOS Pathogens, 14(4), e1006991. DOI: 10.1371/journal.ppat.1006991

  5. Xu, Y., Lewandowski, K., Lumley, S., Pullan, S., Vipond, R., Carroll, M., Foster, D., Matthews, P., Peto, T. and Crook, D. 2018. Detection of Viral Pathogens With Multiplex Nanopore MinION Sequencing: Be Careful With Cross-Talk. Frontiers in Microbiology, 9, e2225. DOI: 10.3389/fmicb.2018.02225

 

Prepared by Callum Robertson

October 2019

January 2020