Virology Unit

Virology Unit


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Cullinane A.,Virology Unit | Elton D.,Center for Preventive Medicine | Mumford J.,Cambridge Infectious Diseases Consortium
Influenza and other Respiratory Viruses | Year: 2010

Please cite this paper as: Cullinane et al. (2010) Equine influenza - surveillance and control. Influenza and Other Respiratory Viruses 4(6), 339-344. Equine influenza virus (EIV) is considered the most important respiratory virus of horses because it is highly contagious and has the potential to disrupt major equestrian events. Equine influenza (EI) can be controlled by vaccination but it has been demonstrated repeatedly in the field that antigenic drift impacts on vaccine efficacy. EI surveillance maintains awareness of emergence and international spread of antigenic variants. It not only serves as an early warning system for horse owners, trainers and veterinary clinicians but is fundamental to influenza control programmes based on vaccination. Data on outbreaks of EI and strain characterisation is reviewed annually by an Expert Surveillance Panel (ESP) including representatives from OIE and WHO. This panel makes recommendations on the need to update vaccines based on analysis of evidence of disease in well vaccinated horses, antigenic changes, genetic changes and when possible, experimental challenge data. However, the disparity in the level of surveillance and virus collection in different countries results in potentially biased information about the relative prevalence of different viruses. There is a need for increased surveillance on a global level and a greater awareness of the benefits of updating the vaccines. The vaccine companies have traditionally been slow to respond to the ESP recommendations. Veterinary clinicians have a major role to play in purchasing vaccines with epidemiologically relevant strains and promoting their benefits to their clients. © 2010 Blackwell Publishing Ltd.


Baldanti F.,Virology Unit | Baldanti F.,Experimental Research Laboratory | Paolucci S.,Virology Unit | Gulminetti R.,Experimental Research Laboratory | And 4 more authors.
Journal of Medical Virology | Year: 2010

The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5-22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4 + T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase geneswere performed at baseline and after 1, 2, 3, 6, and 12months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range118-407,107) to<50 copies/ml (range< 50-7,562), while median CD4 + T-cell counts remained unchanged (from 212 cells/ml, range 10-764 to 262 cells/μl, range 13-760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1month after initiating salvage HAART. Of note, the E→G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additionalmutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1month after initiating HAART salvage regimens. A newmutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated. © 2009 Wiley-Liss, Inc.


Gildea S.,Virology Unit | Arkins S.,University of Limerick | Walsh C.,Trinity College Dublin | Cullinane A.,Virology Unit
Vaccine | Year: 2011

Protection against equine influenza virus (EIV) relies largely on the production of circulating antibodies specific for the haemagglutinin (HA) glycoprotein. The objective of this study was to determine the antibody response of National Hunt horses in training to booster vaccination. The antibody response to the six equine influenza vaccines available in Ireland (three whole inactivated vaccines, two subunit vaccines and a canary pox recombinant vaccine), was monitored by single radial haemolysis (SRH) for six months post vaccination. There was no significant difference between antibody response induced following booster vaccination with any of the six vaccines. The antibodies peaked between two and four weeks post vaccination, decreased significantly by three months post vaccination and declined to their original levels by six months post vaccination. Peak antibody response to the canary pox recombinant vaccine was delayed in comparison to the other vaccines. Although analysis of the mean SRH levels of the horses suggested that they were clinically protected post booster vaccination, analysis of the individual responses suggested that there was potential for vaccination breakdown in a manner similar to that observed previously in racing yards in Ireland. There was a significant correlation between the SRH level at the time of vaccination and the antibody response. The findings of the study suggest that it would be advantageous to monitor SRH levels and to vaccinate strategically. The revaccination of horses with low antibody levels three months post booster vaccination may have been more effective in protecting horses in this yard than the annual vaccination of horses with high SRH levels. Eighteen of the 44 (41%) horses included in this study did not demonstrate a significant rise in SRH level to H3N8 following booster vaccination. It is presumed that annual revaccination is the minimum necessary to protect all horses against EI but this assumption needs to be systematically evaluated. It has been demonstrated that shorter intervals are required for optimum protection of young horses and it may be that longer vaccination intervals are sufficient for older horses with several years of vaccination history. Further investigations in a larger population of horses will be necessary to determine if the findings of this study are applicable to the population at large. © 2011 Elsevier Ltd.


Quint K.D.,Leiden University | Quint K.D.,DDL Diagnostic Laboratory | Genders R.E.,Leiden University | De Koning M.N.C.,DDL Diagnostic Laboratory | And 5 more authors.
Journal of Pathology | Year: 2015

Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the development of mucosal carcinomas at different body sites (eg cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs; basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Focosi D.,North Western Tuscany Blood Bank | Pistello M.,University of Pisa | Pistello M.,Virology Unit
Stem Cells Translational Medicine | Year: 2016

Population aging has imposed cost-effective alternatives to blooddonations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cellsmust be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stemcell (iPSC) technology could pave theway to a newera in transfusionmedicine, just as it is alreadydoing inmany other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. © AlphaMed Press 2016.


Gildea S.,Virology Unit | Arkins S.,University of Limerick | Cullinane A.,Virology Unit
Influenza and other Respiratory Viruses | Year: 2010

Please cite this paper as: Gildea et al. (2010) A comparative antibody study of the potential susceptibility of Thoroughbred and non-Thoroughbred horse populations in Ireland to equine influenza virus. Influenza and Other Respiratory Viruses 4(6), 363-372. Background In Ireland, horses may be protected against equine influenza virus (EIV) as a result of natural exposure or vaccination. Current mandatory vaccination programmes are targeted at highly mobile horses. A correlation between antibody levels as measured by single radial haemolysis (SRH) and protective immunity against EIV has been established. Objectives The objective of this study was to determine the susceptibility of selected populations of horses by quantifying their antibodies to EIV. Methods Blood samples were collected from Thoroughbred weanlings, yearlings, racehorses and broodmares, teaser stallions and non-Thoroughbred horses. Antibodies against EIV H3N8 and H7N7 were measured by SRH. Results The order of susceptibility to Equine Influenza (EI) in the populations examined in Ireland was as follows: Thoroughbred weanlings>teasers>non-Thoroughbred horses and ponies>Thoroughbred yearlings>Thoroughbred horses in training>Thoroughbred broodmares. The H3N8 antibody levels of the weanlings, yearlings, broodmares and horses in training were similar to their H7N7 antibody levels, suggesting that their antibodies were primarily vaccinal in origin. The teasers and non-Thoroughbreds had higher H3N8 antibody levels than H7N7 antibody levels, suggesting that the majority of seropositive horses in these populations had been exposed to H3N8 by natural infection. Conclusions Weanlings, teasers and non-Thoroughbred horses were identified as most susceptible to EIV. The results suggest that it would be advisable that weanlings are vaccinated prior to attendance at public sales, that teaser stallions are vaccinated prior to each breeding season and that mandatory vaccination be implemented for participation in non-Thoroughbred events. © 2010 Blackwell Publishing Ltd.


Memish Z.A.,Ministry of Health | Assiri A.M.,Ministry of Health | Hussain R.,Virology Unit | Alomar I.,Administration of Laboratories and Blood Banks | Stephens G.,Saudi Ministry of Health
Journal of Travel Medicine | Year: 2012

Background. The objectives of this study were to determine whether pilgrim attendance at the Hajj was associated with an increased risk of acquiring influenza, and other respiratory viruses, and to evaluate the compliance of pilgrims with influenza vaccination and other recommended preventive measures. Methods. A cross-sectional survey was conducted among pilgrims as they arrived at the King Abdulaziz International Airport in Jeddah for the 2009 Hajj and as they departed from the same airport during the week after the Hajj. Nasopharyngeal and throat swabs were tested for 18 respiratory virus types and subtypes using the xTAG Respiratory Viral Panel FAST assay. Results. A total of 519 arriving pilgrims and 2,699 departing pilgrims were examined. Their mean age was 49 years and 58% were male. In all, 30% of pilgrims stated that they had received pandemic influenza A(H1N1) vaccine before leaving for the Hajj and 35% of arriving pilgrims reported wearing a face mask. Only 50% of arriving pilgrims were aware of preventive measures such as hand hygiene and wearing a mask. The prevalence of any respiratory-virus infection was 14.5% (12.5% among arriving pilgrims and 14.8% among departing pilgrims). The main viruses detected (both groups combined) were rhinovirus-enterovirus (N = 414, 12.9%), coronaviruses (N = 27, 0.8%), respiratory syncytial virus (N = 8, 0.2%), and influenza A virus (N = 8, 0.2%) including pandemic influenza A(H1N1) (N = 3, 0.1%). The prevalence of pandemic influenza A(H1N1) was 0.2% (N = 1) among arriving pilgrims and 0.1% (N = 2) among departing pilgrims. The prevalence of any respiratory virus infection was lower among those who said they received H1N1 vaccine compared to those who said they did not receive it (11.8% vs 15.6%, respectively, p = 0.009). Conclusion. We found very low pandemic influenza A(H1N1) prevalence among arriving pilgrims and no evidence that amplification of transmission had occurred among departing pilgrims. © 2011 International Society of Travel Medicine.


Pawelek K.A.,Oakland University | Huynh G.T.,Oakland University | Quinlivan M.,Virology Unit | Cullinane A.,Virology Unit | And 2 more authors.
PLoS Computational Biology | Year: 2012

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.


Gildea S.,Virology Unit | Fitzpatrick D.A.,National University of Ireland, Maynooth | Cullinane A.,Virology Unit
Influenza and other Respiratory Viruses | Year: 2013

Background: Outbreaks of equine influenza (EI) in endemic populations cause disruption and economic loss. Objectives: To identify (i) factors involved in the spread of EI (ii) virus strains responsible for outbreaks (iii) single radial haemolysis (SRH) antibody levels correlating with protection against current virus strains (iv) evidence of vaccination breakdown. Methods: RT-PCR, virus isolation and SRH were carried out on nasopharyngeal swabs and blood samples collected from horses, ponies and donkeys on affected premises. Data relating to 629 samples from 135 equidae were analysed. Results and conclusions: Outbreaks were sporadic, self limiting and associated with the movement of horses. Vaccination status and age influenced clinical signs of disease while housing and fomites contributed to virus spread. Subclinical infection as defined as a horse which tested positive by one or more of the following; RT-PCR, virus isolation and seroconversion in the absence of clinical signs, was identified in 9% of animals. Of the horses with up to date vaccination records 32% developed clinical signs. Vaccine breakdown occurred among horses vaccinated with all four commercially available vaccines. Analysis of HA1 sequence data generated for 26 viruses indicated that they all belonged to clade 2 of the Florida sublineage. Higher SRH antibody levels were required for both clinical and virological protection than reported in studies where vaccine strains were antigenically and genetically similar to those circulating in the field. The results of this study therefore support the OIE recommendations that vaccines be updated to include representatives of both clades of the Florida sublineage. © 2013 Blackwell Publishing Ltd.


Antignus Y.,Virology Unit
Advances in Virus Research | Year: 2012

Viral pathogens form an important group of obligatory parasites of plants. About 977 plant viruses have been described and classified in 14 families and 70 genera. This group of pathogens has complex interactions with their host plants and vectors due to their integration in the molecular mechanisms of living cells, interfering with our ability to manage the malfunctions of virus infected plants by curing means. These constraints led to the perception that the best protection from virus diseases is by prevention. Many cultural procedures used for virus control are aimed at eradicating or altering one or more of the primary participants in the transmission process (vector, virus source plants, and the crop) or preventing their coming together. Part of these control measures were devised to reduce to a minimum, the number of inoculative vector individuals that are active in the crop or interfere with the transmission process at any of its phases, thereby arresting virus spread. Advances in plant virology and a better understanding of plant vector interactions provide strategies based on the formation of mechanical and optical barriers that interfere with the ability of the viral pathogen or its vector to reach the plant and initiate an epidemic. © 2012 Elsevier Inc.

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