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

There were a total of 2609 results for your search.
Batten C A, Edwards L, Oura C A L (2013)

Evaluation of the humoral immune responses in adult cattle and sheep, 4 and 2.5 years post-vaccination with a bluetongue serotype 8 inactivated vaccine

Vaccine 31 (37), 3783-3785
Publisher’s version: http://dx.doi.org/10.1016/j.vaccine.2013.06.033

Abstract

One of the big surprises about the devastating outbreak of bluetongue serotype-8 that spread across Northern and Western Europe between 2006 and 2008 was how relatively quickly the virus was controlled and eradicated from affected countries. This was at least in part attributed to the high levels of vaccine coverage achieved in affected countries. A previous study revealed that neutralising antibodies persisted in the majority of vaccinated cattle for at least 3 years post-vaccination, indicating that cattle are likely to be protected for this time period. The current study revealed that neutralising antibodies persisted in the same group of cattle for up to 4 years post-vaccination, and that neutralising antibodies persisted for up to 2.5 years in sheep that had been vaccinated on two occasions one year apart. These results have implications for future bluetongue surveillance programmes and vaccine control strategies.
Batten C A, Henstock M R, Steedman H M, Waddington S, Edwards L, Oura C A L (2013)

Bluetongue virus serotype 26: Infection kinetics, pathogenesis and possible contact transmission in goats

Veterinary Microbiology 162 (1), 62-67
Publisher’s version: http://dx.doi.org/10.1016/j.vetmic.2012.08.014

Abstract

The aim of this study was to assess the pathogenicity and infection kinetics of Bluetongue virus serotype 26 (BTV-26) in goats. Out of a group of six goats housed in insect free accommodation, five were experimentally infected with BTV-26 and one was kept uninfected as an in-contact control. Samples taken throughout the study were used to determine the kinetics of infection using a pan specific BTV real time RT-PCR assay and a group specific ELISA. The five infected goats did not show clinical signs of BTV, however high levels of viral RNA were detected and virus was isolated from the blood of all 5 goats. Antibodies against BTV were first detected between 7 and 11 dpi in all 5 experimentally infected goats. Interestingly at 21 dpi viral RNA was detected in, and virus was isolated from, the blood of the in-contact control goat, which also seroconverted. These results suggest that BTV-26 replicates to high levels in goats, causing no obvious clinical disease, suggesting that goats may be the natural host for this virus. Preliminary evidence also indicates that BTV-26 may be spread by contact transmission between goats, however a more detailed study is required in order to confirm this observation.
Belaganahalli M N, Maan S, Maan N S, Nomikou K, Guimera M, Brownlie J, Tesh R, Attoui H, Mertens P P C (2013)

Full genome sequencing of Corriparta virus, identifies California mosquito pool virus as a member of the Corriparta virus species

PLoS ONE 8 (8), e70779
Publisher’s version: http://dx.doi.org/10.1371/journal.pone.0070779

Abstract

The species Corriparta virus (CORV), within the genus Orbivirus, family Reoviridae, currently contains six virus strains: corriparta virus MRM1 (CORV-MRM1); CS0109; V654; V370; Acado virus and Jacareacanga virus. However, lack of neutralization assays, or reference genome sequence data has prevented further analysis of their intra-serogroup/species relationships and identification of individual serotypes. We report whole-genome sequence data for CORV-MRM1, which was isolated in 1960 in Australia. Comparisons of the conserved, polymerase (VP1), sub-core-shell 'T2' and core-surface 'T13' proteins encoded by genome segments 1, 2 and 8 (Seg-1, Seg-2 and Seg-8) respectively, show that this virus groups with the other mosquito borne orbiviruses. However, highest levels of nt/aa sequence identity (75.9%/91.6% in Seg-2/T2: 77.6%/91.7% in Seg-8/T13, respectively) were detected between CORV-MRM1 and California mosquito pool virus (CMPV), an orbivirus isolated in the USA in 1974, showing that they belong to the same virus species. The data presented here identify CMPV as a member of the Corriparta virus species and will facilitate identification of additional CORV isolates, diagnostic assay design and epidemiological studies.
Bell-Sakyi L, Attoui H (2013)

Endogenous tick viruses and modulation of tick-borne pathogen growth

Frontiers in Cellular and Infection Microbiology 3, 25
Publisher’s version: http://dx.doi.org/10.3389/fcimb.2013.00025

Abstract

Ticks transmit a wide range of viral, bacterial and protozoan pathogens, many of which can establish persistent infections of lifelong duration in the vector tick and in some cases are transmitted transovarially to the next generation. In addition many ixodid and argasid tick cell lines and, by inference the parent ticks from which they were derived, harbor endogenous viruses (ETV) of which almost nothing is known. In general, low level persistent infections with viral pathogens (arboviruses) are not known to have a deleterious effect on tick survival and fitness, suggesting that they can strike a balance with the tick innate immune response. This tolerance of arbovirus infection may be modulated by the permanent presence of ETV in the host cell. In mosquito cells, temporary or permanent silencing of the genes of an endogenous virus by RNA interference can result in changes in replication rate of a co-infecting arbovirus. We propose that tick cell lines offer a useful model system for in vitro investigation of the modulatory effect of ETV on superinfecting pathogen survival and replication in ticks, using the molecular manipulation techniques applied to insect cells.
Kirunda H, Kabi F, Muwereza N, Kabuuka T, Magona J W, Lukwago G (2012)

Knowledge and perceptions of smallholder dairy farmers of cattle disease burdens in selected agro-ecological zones of Uganda

Uganda Journal of Agricultural Sciences 13 (2), 107-116
Publisher’s version: https://www.ajol.info/index.php/ujas/article/view/126213

Abstract

Diseases have continued to affect production and productivity in smallholder dairy farming systems in Uganda. This study sought to establish farmers knowledge and perceptions of disease burden in the Eastern Semi-Arid Zone (ESAZ), Lake Victoria Basin (LVB) and Western Rangelands (WR) agro-ecological zones (AEZs). A structured questionnaire was administered to 150 farm household heads or cattle attendants. Data analysis by cross tabulations was done using SPSS Statistical Software and descriptive statistics generated in XLSTAT. Linear Discriminant analysis and Multivariate Analysis of Variance were computed to establish significant relationships (P<0.05) between variables. East Coast fever (ECF), calf scours, foot rot, mastitis and fascioliasis were reported of high prevalence (>50%), while brucellosis and eye infection had low prevalence (<16.7%). Season, age and breed of cattle were significantly associated with severity, morbidity, mortality and treatment costs in all AEZs. Morbidity and mortality were higher during the long (4.5; 0.7) than short rains (3.1; 0.6), respectively. Comparatively, average treatment costs were higher during the short rains (US$ 22) compared to long rains (US$ 17) each rains lasting three months. Results of our study show that some diseases were common to all AEZs, yet ESAZ had a higher disease burden than WR and LVB.

Dhote V, Sweeney T R, Kim N, Hellen C U, Pestova T V (2012)

Roles of individual domains in the function of DHX29, an essential factor required for translation of structured mammalian mRNAs

Proceedings of the National Academy of Sciences U S A 109 (46), E3150-3159
Publisher’s version: https://doi.org/10.1073/pnas.1208014109

Abstract

On most eukaryotic mRNAs, initiation codon selection involves base-by-base inspection of 5′ UTRs by scanning ribosomal complexes. Although the eukaryotic initiation factors 4A/4B/4G can mediate scanning through medium-stability hairpins, scanning through more stable structures additionally requires DHX29, a member of the superfamily 2 DEAH/RNA helicase A (RHA) helicase family that binds to 40S subunits and possesses 40S-stimulated nucleoside triphosphatase (NTPase) activity. Here, sequence alignment and structural modeling indicated that DHX29 comprises a unique 534-aa–long N-terminal region (NTR), central catalytic RecA1/RecA2 domains containing a large insert in the RecA2 domain, and the C-terminal part, which includes winged-helix, ratchet, and oligonucleotide/oligosaccharide-binding (OB) domains that are characteristic of DEAH/RHA helicases. Functional characterization revealed that specific ribosomal targeting is required for DHX29’s activity in initiation and is determined by elements that map to the NTR and to the N-terminal half of the winged-helix domain. The ribosome-binding determinant located in the NTR was identified as a putative double-stranded RNA-binding domain. Mutational analyses of RecA1/RecA2 domains confirmed the essential role of NTP hydrolysis for DHX29’s function in initiation and validated the significance of a β-hairpin protruding from RecA2. The large RecA2 insert played an autoinhibitory role in suppressing DHX29’s intrinsic NTPase activity but was not essential for its 40S-stimulated NTPase activity and function in initiation. Deletion of the OB domain also increased DHX29's basal NTPase activity, but more importantly, abrogated the responsiveness of the NTPase activity to stimulation, which abolished DHX29's function in initiation. This finding suggests that the OB domain, which is specific for DEAH/RHA helicases, plays an important role in their NTPase cycle.

Sweeney T R, Dhote V, Yu Y, Hellen C U (2012)

A distinct class of internal ribosomal entry site in members of the Kobuvirus and proposed Salivirus and Paraturdivirus genera of the Picornaviridae

Journal of Virology 86 (3), 1468-1486
Publisher’s version: https://doi.org/10.1128/jvi.05862-11

Abstract

The 5?-untranslated regions (5' UTRs) of picornavirus genomes contain an internal ribosomal entry site (IRES) that promotes the end-independent initiation of translation. Picornavirus IRESs are classified into four structurally distinct groups, each with different initiation factor requirements. Here, we identify a fifth IRES class in members of Kobuvirus, Salivirus, and Paraturdivirus genera of Picornaviridae: Aichi virus (AV), bovine kobuvirus (BKV), canine kobuvirus (CKoV), mouse kobuvirus (MKoV), sheep kobuvirus (SKV), salivirus A (SV-A), turdivirus 2 (TV2), and TV3. The 410-nucleotide (nt)-long AV IRES comprises four domains (I to L), including a hairpin (L) that overlaps a Yn-Xm-AUG (pyrimidine tract/spacer/initiation codon) motif. SV-A, CKoV, and MKoV also contain these four domains, whereas BKV, SKV, and TV2/TV3 5' UTRs contain domains that are related to domain I and equivalent to domains J and K but lack an AV-like domain L. These IRESs are located at different relative positions between a conserved 5?-terminal origin of replication and divergent coding sequences. Elements in these IRESs also occur elsewhere: domain J's apical subdomain, which contains a GNRA tetraloop, matches an element in type 1 IRESs, and eIF4G-binding motifs in domain K and in type 2 IRESs are identical. Other elements are unique, and their presence leads to unique initiation factor requirements. In vitro reconstitution experiments showed that like AV, but in contrast to other currently characterized IRESs, SV-A requires the DExH-box protein DHX29 during initiation, which likely ensures that the initiation codon sequestered in domain L is properly accommodated in the ribosomal mRNA-binding cleft.

Aguirre S, Maestre A M, Pagni S, Patel J R, Savage T, Gutman D, Maringer K, Bernal-Rubio D, Shabman R S, Simon V, Rodriguez-Madoz J R, Mulder L C, Barber G N, Fernandez-Sesma A (2012)

DENV inhibits type I IFN production in infected cells by cleaving human STING

PLoS Pathogens 8 (10), e1002934
Publisher’s version: https://doi.org/10.1371/journal.ppat.1002934

Abstract

Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.

Maringer K, Stylianou J, Elliott G (2012)

A network of protein interactions around the herpes simplex virus tegument protein VP22

Journal of Virology 86 (23), 12971-12982
Publisher’s version: https://doi.org/10.1128/JVI.01913-12

Abstract

Assembly of the herpesvirus tegument is poorly understood but is believed to involve interactions between outer tegument proteins and the cytoplasmic domains of envelope glycoproteins. Here, we present the detailed characterization of a multicomponent glycoprotein-tegument complex found in herpes simplex virus 1 (HSV-1)-infected cells. We demonstrate that the tegument protein VP22 bridges a complex between glycoprotein E (gE) and glycoprotein M (gM). Glycoprotein I (gI), the known binding partner of gE, is also recruited into this gE-VP22-gM complex but is not required for its formation. Exclusion of the glycoproteins gB and gD and VP22's major binding partner VP16 demonstrates that recruitment of virion components into this complex is highly selective. The immediate-early protein ICP0, which requires VP22 for packaging into the virion, is also assembled into this gE-VP22-gM-gI complex in a VP22-dependent fashion. Although subcomplexes containing VP22 and ICP0 can be formed when either gE or gM are absent, optimal complex formation requires both glycoproteins. Furthermore, and in line with complex formation, neither of these glycoproteins is individually required for VP22 or ICP0 packaging into the virion, but deletion of gE and gM greatly reduces assembly of both VP22 and ICP0. Double deletion of gE and gM also results in small plaque size, reduced virus yield, and defective secondary envelopment, similar to the phenotype previously shown for pseudorabies virus. Hence, we suggest that optimal gE-VP22-gM-gI-ICP0 complex formation correlates with efficient virus morphogenesis and spread. These data give novel insights into the poorly understood process of tegument acquisition.

Benlahrech A, Yasmin A, Westrop S J, Coleman A, Herasimtschuk A, Page E, Kelleher P, Gotch F, Imami N, and Patterson S (2012)

Dysregulated immunophenotypic attributes of plasmacytoid but not myeloid dendritic cells in HIV-1 infected individuals in the absence of highly active anti-retroviral therapy

Clinical and Experimental Immunology 170 (2), 212-221
Publisher’s version: https://doi.org/10.1111/j.1365-2249.2012.04647.x

Abstract

Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1+ patients. DC from healthy controls, untreated HIV-1+ and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1+ patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1+patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.

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