The Pirbright Institute publication directory contains details of selected publications written by our researchers.

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Nicol M Q, Campbell G M, Shaw D J, Dransfield I, Ligertwood Y, Beard P M, Nash A A, Dutia B M (2019)

Lack of IFNγ signaling attenuates spread of influenza A virus in vivo and leads to reduced pathogenesis

Virology 526, 155-164


IFNγ is a key regulator of inflammatory responses but its role in influenza A virus (IAV) pathogenesis is unclear. Our studies show that infection of mice lacking the IFNγ receptor (IFNγR-/-) at a dose which caused severe disease in wild type 129Sv/Ev (WT) mice resulted in milder clinical symptoms and significantly lower lung virus titers by 6 days post-infection (dpi). Viral spread was reduced in IFNγR-/- lungs at 2 and 4 dpi. Levels of inflammatory cytokines and chemokines were lower in IFNγR-/- mice at 2 dpi and there was less infiltration of monocyte/macrophage lineage cells than in WT mice. There was no difference in CD4+ and CD8+ T cells and alveolar macrophages in the bronchoalveolar lavage fluid (BALF) at 2 and 4 dpi but by 4 dpi IFNγR-/- mice had significantly higher percentages of neutrophils. Our data strongly suggest that IAV can use the inflammatory response to promote viral spread.

Maan S, Belaganahalli M N, Maan N S, Potgieter A C, Mertens P P C (2018)

Quantitative RT-PCR assays for identification and typing of the Equine encephalosis virus

Brazilian Journal of Microbiology early view,


Equine encephalosis (EE) is an acute, arthropod-borne, noncontagious, febrile disease of equids. The clinical signs of EE are similar to milder forms of African horse sickness (AHS) and the two diseases can be easily confused. The Equine encephalosis virus (EEV) is a distinct virus species within the genus Orbivirus, family Reoviridae, with ten linear segments of dsRNA genome. Seven distinct serotypes of EEV have been recognised on the basis of sequence analyses of Seg-2. The need for differential diagnosis of similar forms of EE and AHS warranted the development of molecular diagnostic methods for specific detection and identification of EEV. We report the development of quantitative real-time RT-PCR assay for detection of any member of the EEV species targeting the highly conserved EEV Seg-9. Similar serotype-specific qRT-PCR assays were designed for each of the seven EEV serotypes targeting genome Seg-2, encoding the serotype determining VP2 protein. These assays were evaluated using different EEV serotypes and other closely related orbiviruses. They were shown to be EEV virus species–specific, or EEV type–specific capable of detecting 1 to 13 copies of viral RNA in clinical samples. The assays failed to detect RNA from closely related orbiviruses, including AHSV and Peruvian horse sickness virus (PHSV) isolates.

Huang K-Y A, Rijal P, Jiang H, Wang B, Schimanski L, Dong T, Liu Y-M, Chang P, Iqbal M, Wang M-C, Chen Z, Song R, Huang C-C, Yang J-H, Qi J, Lin T-Y, Li A, Powell T J, Jan J-T, Ma C, Gao G F, Shi Y, Townsend A R (2018)

Structure–function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans

Nature Microbiology early view,


Little is known about the specificities and neutralization breadth of the H7-reactive antibody repertoire induced by natural H7N9 infection in humans. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Of these, 45 antibodies were H7-specific, and 17 of these neutralized the virus, albeit with few somatic mutations in their variable domain sequences. An additional set of 28 antibodies, isolated from younger donors born after 1968, cross-reacted between H7 and H3 haemagglutinins in binding assays, and had accumulated significantly more somatic mutations, but were predominantly non-neutralizing in vitro. Crystal structures of three neutralizing and protective antibodies in complex with the H7 haemagglutinin revealed that they recognize overlapping residues surrounding the receptor-binding site of haemagglutinin. One of the antibodies, L4A-14, bound into the sialic acid binding site and made contacts with haemagglutinin residues that were conserved in the great majority of 2016–2017 H7N9 isolates. However, only 3 of the 17 neutralizing antibodies retained activity for the Yangtze River Delta lineage viruses isolated in 2016–2017 that have undergone antigenic change, which emphasizes the need for updated H7N9 vaccines.

Varjak M, Dietrich I, Sreenu V B, Till B E, Merits A, Kohl A, Schnettler E (2018)

Spindle-E acts antivirally against alphaviruses in mosquito cells

Viruses 10 (2),
Publisher’s version:


Mosquitoes transmit several human- and animal-pathogenic alphaviruses (Togaviridae family). In alphavirus-infected mosquito cells two different types of virus-specific small RNAs are produced as part of the RNA interference response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRNA pathway is generally thought to be the main antiviral pathway. Although an antiviral activity has been suggested for the piRNA pathway its role in host defences is not clear. Knock down of key proteins of the piRNA pathway (Ago3 and Piwi5) in Aedesaegypti-derived cells reduced the production of alphavirus chikungunya virus (CHIKV)-specific piRNAs but had no effect on virus replication. In contrast, knock down of the siRNA pathway key protein Ago2 resulted in an increase in virus replication. Similar results were obtained when expression of Piwi4 was silenced. Knock down of the helicase Spindle-E (SpnE), an essential co-factor of the piRNA pathway in Drosophila melanogaster, resulted in increased virus replication indicating that SpnE acts as an antiviral against alphaviruses such as CHIKV and the related Semliki Forest virus (SFV). Surprisingly, this effect was found to be independent of the siRNA and piRNA pathways in Ae. aegypti cells and specific for alphaviruses. This suggests a small RNA-independent antiviral function for this protein in mosquitoes.

Sealy J E, Yaqub T, Peacock T P, Chang P, Ermetal B, Clements A, Sadeyen J R, Mehboob A, Shelton H, Bryant J E, Daniels R S, McCauley J W, Iqbal M (2018)

Association of increased receptor-binding avidity of influenza A(H9N2) viruses with escape from antibody-based immunity and enhanced zoonotic potential

Emerging Infectious Diseases 25 (1), 63-72


We characterized 55 influenza A(H9N2) viruses isolated in Pakistan during 2014-2016 and found that the hemagglutinin gene is of the G1 lineage and that internal genes have differentiated into a variety of novel genotypes. Some isolates had up to 4-fold reduction in hemagglutination inhibition titers compared with older viruses. Viruses with hemagglutinin A180T/V substitutions conveyed this antigenic diversity and also caused up to 3,500-fold greater binding to avian-like and >20-fold greater binding to human-like sialic acid receptor analogs. This enhanced binding avidity led to reduced virus replication in primary and continuous cell culture. We confirmed that altered receptor-binding avidity of H9N2 viruses, including enhanced binding to human-like receptors, results in antigenic variation in avian influenza viruses. Consequently, current vaccine formulations might not induce adequate protective immunity in poultry, and emergence of isolates with marked avidity for human-like receptors increases the zoonotic risk.

Krzywinska E, Krzywinski J (2018)

Effects of stable ectopic expression of the primary sex determination gene Yob in the mosquito Anopheles gambiae

Parasites and Vectors 11 (2), 648


Mosquito-borne diseases, such as malaria, are controlled primarily by suppressing mosquito vector populations using insecticides. The current control programmes are seriously threatened by the emergence and rapid spread of resistance to approved insecticides. Genetic approaches proposed to complement the existing control efforts may be a more sustainable solution to mosquito control. All such approaches would rely on releases of modified male mosquitoes, because released females would contribute to biting and pathogen transmission. However, no sufficiently large-scale methods for sex separation in mosquitoes exist.

Dalby A R, Tinworth L, Iqbal M (2018)

The genotype diversity within the H5N8 influenza A subtype

bioRxiv , 492470
Publisher’s version:


The H5N8 influenza subtype has been involved in the global spread of the Guangdong variant of the H5 hemagglutinin. The sequence data from all of the complete genomes from the H5N8 subtype was used to analyse the genotype diversity. Clustering analysis was used to assign lineages to each of the segments where different lineages were present. The results show that there have been multiple reassortment events both within the Guangdong and non-Guangdong H5 hemagglutinin containing variants. The Guangdong H5 variants can be subdivided further into two sub-lineages and that have undergone reassortment in both the far east and the United States.

Souley Kouato B, De Clercq K, Abatih E, Dal Pozzo F, King D P, Thys E, Marichatou H, Saegerman C (2018)

Review of epidemiological risk models for foot-and-mouth disease: Implications for prevention strategies with a focus on Africa

PLoS One 13 (12), e0208296


Foot-and-mouth disease (FMD) is a highly infectious transboundary disease that affects domestic and wild cloven-hoofed animal species. The aim of this review was to identify and critically assess some modelling techniques for FMD that are well supported by scientific evidence from the literature with a focus on their use in African countries where the disease remains enzootic. In particular, this study attempted to provide a synopsis of the relative strengths and weaknesses of these models and their relevance to FMD prevention policies. A literature search was conducted to identify quantitative and qualitative risk assessments for FMD, including studies that describe FMD risk factor modelling and spatiotemporal analysis. A description of retrieved papers and a critical assessment of the modelling methods, main findings and their limitations were performed. Different types of models have been used depending on the purpose of the study and the nature of available data. The most frequently identified factors associated with the risk of FMD occurrence were the movement (especially uncontrolled animal movement) and the mixing of animals around water and grazing points. Based on the qualitative and quantitative risk assessment studies, the critical pathway analysis showed that the overall risk of FMDV entering a given country is low. However, in some cases, this risk can be elevated, especially when illegal importation of meat and the movement of terrestrial livestock are involved. Depending on the approach used, these studies highlight shortcomings associated with the application of models and the lack of reliable data from endemic settings. Therefore, the development and application of specific models for use in FMD endemic countries including Africa is encouraged.

Klement E, Broglia A, Antoniou S-E, Tsiamadis V, Plevraki E, Petrovi? T, Pola?ek V, Debeljak Z, Miteva A, Alexandrov T, Marojevic D, Pite L, Kondratenko V, Atanasov Z, Gubbins S, Stegeman A, Abrahantes J C (2018)

Neethling vaccine proved highly effective in controlling lumpy skin disease epidemics in the Balkans

Preventive Veterinary Medicine early view,


Despite the wide use of the live attenuated Neethling lumpy skin disease (LSD) vaccine, only limited data existed on its efficacy and effectiveness prior to the large LSD epidemic in the Balkans, which took place during 2016–2017. In addition, analysis of risk factors for the disease was hardly performed with proper control for vaccination effects and potential differences in exposure to the virus. Data from the LSD epidemics in six Balkan countries (Bulgaria, Greece, Serbia, Montenegro, Former Yugoslav Republic of Macedonia (FYROM) and Albania) affected during 2016 were analyzed to determine vaccine effectiveness (VE) and risk factors for LSD infection at the farm level. Vaccination was performed along the occurrence of the epidemics and thus vaccination status of some of the farms changed during the epidemic. To allow for this, left truncated and right censored survival analysis was used in a mixed effects Cox proportional hazard regression model to calculate VE and risk factors for LSD. The results indicated of an average VE of 79.8% (95% CI: 73.2–84.7)) in the six countries, with the lowest VE of 62.5% documented in Albania and up to VE of more than 97% as documented in Bulgaria and Serbia. Analysis of time from vaccination to development of protective immunity showed that VE mostly developed during the first 14 days after vaccination. Data from Greece showed that the vaccination adjusted hazard ratio for LSD was 5.7 higher in grazing farms compared to non-grazing farms. However, due to a difference in geographical location of grazing and non-grazing farms and higher vaccination rate in non-grazing farms, this effect can be at least partly attributed to indirect protection due to herd immunity provided by surrounding vaccinated farms.


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