Canine Adenovirus Type Research Articles

Isolation and identification of canine adenovirus type 2 from a naturally infected dog in Korea

Isolation and identification of canine adenovirus type 2 from a naturally infected dog in Korea

EXPOSURE OF ALASKA BROWN BEARS (URSUS ARCTOS) TO BACTERIAL, VIRAL, AND PARASITIC AGENTS VARIES SPATIOTEMPORALLY AND MAY BE INFLUENCED BY AGE.

We collected blood and serum from 155 brown bears (Ursus arctos) inhabiting five locations in Alaska, US during 2013-16 and tested samples for evidence of prior exposure to a suite of bacterial, viral, and parasitic agents. Antibody seroprevalence among Alaska brown bears was estimated to be 15% for Brucella spp., 10% for Francisella tularensis, 7% for Leptospira spp., 18% for canine adenovirus type 1 (CAV-1), 5% for canine distemper virus (CDV), 5% for canine parvovirus, 5% for influenza A virus (IAV), and 44% for Toxoplasma gondii. No samples were seropositive for antibodies to Trichinella spp. Point estimates of prior exposure to pathogens among brown bears at previously unsampled locations generally fell within the range of estimates for previously or contemporaneously sampled bears in Alaska. Statistical support was found for variation in antibody seroprevalence among bears by location or age cohort for CAV-1, CDV, IAV, and T. gondii. There was limited concordance in comparisons between our results and previous serosurveys regarding spatial and age-related trends in antibody seroprevalence among Alaska brown bears suggestive of temporal variation. However, we found evidence that the seroprevalence of CAV-1 antibodies is consistently high in bears inhabiting southwest Alaska and the cumulative probability of exposure may increase with age. We found evidence for seroconversion or seroreversion to six different infectious agents in one or more bears. Results of this study increase our collective understanding of disease risk to both Alaska brown bear populations and humans that utilize this resource.

Canine adenovirus type 1 (CAdV-1) in free-ranging European brown bear (Ursus arctos arctos ): A threat for Cantabrian population?

Canine adenovirus type 1 (CAdV-1) is responsible for infectious canine hepatitis. The disease has been described in captive American black bear (Ursus americanus) and European brown bear (Ursus arctos arctos), with just one recently reported case in a cub of a free-ranging brown bear (Ursus arctos horribilis) from Alaska. The aim of this work is to summarize findings related to presence and associated mortality of CAdV-1 in 21 free-ranging Cantabrian brown bears (Ursus arctos arctos) submitted to necropsy in Asturias and Castilla y León (northwestern Spain) from 1998 to 2018. On the basis of the anatomopathological findings and laboratory results three free-ranging brown bears died due to infectious canine hepatitis, which is to our knowledge the first description of death due to this disease in free-ranging bears in Europe. Gross lesions consisted of petechial haemorrhages and congestion in different internal organs, haemorrhagic fluid in internal cavities, friable and yellowish liver and thickening of gall bladder. Microscopic lesions were observed mainly in liver, kidney and brain and consisted of multifocal necrosis of cells with presence of basophilic intranuclear inclusions. Immunohistochemical (IHC) and real-time polymerase chain reaction (qPCR) techniques were used to assess the presence of CAdV-1 in paraffin-embedded liver samples. Viral antigens were detected by IHC labelling within hepatocytes and Küppfer cells in the three animals. The presence of viral DNA was confirmed by qPCR in one of them. In order to evaluate the circulation of CAdV-1 in brown bears, a retrospective study was performed using both IHC and qPCR techniques in 11 and 12 additional brown bears, respectively. An extra brown bear was found positive by IHC. This study shows that CAdV-1 surveillance of brown bears and sympatric carnivores should be considered as major concern for the monitoring the population evolution throughout time in this endangered species.

Exogenous LRRK2G2019S induces parkinsonian-like pathology in a nonhuman primate.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among the elderly. To understand its pathogenesis and to test therapies, animal models that faithfully reproduce key pathological PD hallmarks are needed. As a prelude to developing a model of PD, we tested the tropism, efficacy, biodistribution, and transcriptional effect of canine adenovirus type 2 (CAV-2) vectors in the brain of Microcebus murinus, a nonhuman primate that naturally develops neurodegenerative lesions. We show that introducing helper-dependent (HD) CAV-2 vectors results in long-term, neuron-specific expression at the injection site and in afferent nuclei. Although HD CAV-2 vector injection induced a modest transcriptional response, no significant adaptive immune response was generated. We then generated and tested HD CAV-2 vectors expressing leucine-rich repeat kinase 2 (LRRK2) and LRRK2 carrying a G2019S mutation (LRRK2G2019S), which is linked to sporadic and familial autosomal dominant forms of PD. We show that HD-LRRK2G2019S expression induced parkinsonian-like motor symptoms and histological features in less than 4 months.

Detection and molecular characterization of canine adenovirus type 2 (CAV-2) in dogs with respiratory tract symptoms in shelters in Turkey

Detection and molecular characterization of canine adenovirus type 2 (CAV-2) in dogs with respiratory tract symptoms in shelters in Turkey

A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons

Retrogradely transported neurotropic viruses enable genetic access to neurons based on their long-range projections and have become indispensable tools for linking neural connectivity with function. A major limitation of viral techniques is that they rely on cell-type-specific molecules for uptake and transport. Consequently, viruses fail to infect variable subsets of neurons depending on the complement of surface receptors expressed (viral tropism). We report a receptor complementation strategy to overcome this by potentiating neurons for the infection of the virus of interest-in this case, canine adenovirus type-2 (CAV-2). We designed AAV vectors for expressing the coxsackievirus and adenovirus receptor (CAR) throughout candidate projection neurons. CAR expression greatly increased retrograde-labeling rates, which we demonstrate for several long-range projections, including some resistant to other retrograde-labeling techniques. Our results demonstrate a receptor complementation strategy to abrogate endogenous viral tropism and thereby facilitate efficient retrograde targeting for functional analysis of neural circuits.

A canine adenovirus type 2 vaccine vector confers protection against foot-and-mouth disease in guinea pigs

Vaccination is a key element in the control of foot-and-mouth disease (FMD). The majority of the antigenic sites that induce protective immune responses are localized on the FMD virus (FMDV) capsid that is formed by four virus-encoded structural proteins, VP1 to VP4. In the present study, recombinant canine adenovirus type 2 (CAV2)-based FMD vaccines, Cav-P1/3C R° and Cav-VP1 R°, respectively expressing the structural P1 precursor protein along with the non-structural 3C protein or expressing the structural VP1 protein of the FMDV strain O/FRA/1/2001, were evaluated as novel vaccines against FMD. A strong humoral immune response was elicited in guinea pigs (GP) following immunization with Cav-P1/3C R°, while administration of Cav-VP1 R° did not induce a satisfying antibody response in GP or mice. GP were then used as an experimental model for the determination of the protection afforded by the Cav-P1/3C R° vaccine against challenge with the FMDV strain O1 Manisa/Turkey/1969. The Cav-P1/3C R° vaccine protected GP from generalized FMD to a similar extent as a high potency double-oil emulsion O1 Manisa vaccine. The results of the present study show that CAV2-based vector vaccines can express immunogenic FMDV antigens and offer protection against generalized FMD in GP. This suggest that Cav-P1/3C R° FMDV vaccine may protect natural host species from FMD. In combination with an appropriate diagnostic test, the Cav-P1/3C R° FMDV vaccine may also serve as a marker vaccine to differentiate vaccinated from infected animals.

A screening for canine distemper virus, canine adenovirus and carnivore protoparvoviruses in Arctic foxes (Vulpes lagopus) and red foxes (Vulpes vulpes) from Arctic and sub-Arctic regions of Norway

ABSTRACTCanine distemper virus (CDV), canine adenovirus (CAdV) and canine parvovirus type 2 (CPV-2) cause disease in dogs (Canis familiaris). These, or closely related viruses, may also infect wild...

Incidence and Sero-survey of Canine Adenovirus Type 2 in Various Animal Species

Incidence and Sero-survey of Canine Adenovirus Type 2 in Various Animal Species

Recombinant canine adenovirus type 2 expressing rabbit hemorrhagic disease virus VP60 protein provided protection against RHD in rabbits

Rabbit hemorrhagic disease virus (RHDV) is responsible for rabbit hemorrhagic disease (RHD), which is an acute, lethal and highly contagious disease in both wild and domestic rabbits. Although current vaccines are highly effective for controlling RHD, they are derived from infected rabbit livers and their use is thus associated with safety and animal-welfare concerns. In this study, we generated a recombinant lentogenic canine adenovirus type 2 (CAV2) vector expressing the RHDV vp60 gene, named rCAV2-VP60. rCAV2-VP60 expressed VP60 protein in Madin–Darby canine kidney cells as demonstrated by western blot and immunofluorescence assay. Polymerase chain reaction confirmed that the vp60 gene was successfully inserted into rCAV2-VP60 and was still detectable after 20 passages, indicating its stable genetic character. We evaluated the feasibility of rCAV2-VP60 as a live-virus-vectored RHD vaccine in rabbits. rCAV2-VP60 significantly induced specific antibodies to RHDV and provided effective protection against RHDV lethal challenge. These results suggest that rCAV2 expressing RHDV VP60 could be a safe and efficient candidate vaccine against RHDV in rabbits.

Long-lived immunity to canine core vaccine antigens in UK dogs as assessed by an in-practice test kit.

To determine the utility of an in-practice test kit to detect protective serum antibody against canine distemper virus, canine adenovirus and canine parvovirus type 2 in a sample of the UK dog population. Serum samples from 486 dogs, last vaccinated between less than 1 month and 124 months previously, were tested with the VacciCheck™ test kit for protective antibodies against distemper, adenovirus and parvovirus type 2. A high proportion of the dogs tested (93·6%) had protective antibody against all three of the core vaccine antigens: 95·7% of the dogs were seropositive against canine distemper virus, 97·3% against canine adenovirus and 98·5% against canine parvovirus type 2. The small number of dogs that were seronegative for one or more of the antigens (n = 31) may have had waning of previous serum antibody or may have been rare genetic non-responders to that specific antigen. UK veterinarians can be reassured that triennial revaccination of adult dogs with core vaccines provides long-lived protective immunity. In-practice serological test kits are a valuable tool for informing decision-making about canine core revaccination.

Evaluation of protective efficacy of three novel H3N2 canine influenza vaccines.

Canine influenza virus (CIV) has the potential risk to spread in different areas and dog types. Thus, there is a growing need to develop an effective vaccine to control CIV disease. Here, we developed three vaccine candidates: 1) a recombinant pVAX1 vector expressing H3N2 CIV hemagglutinin (pVAX1-HA); 2) a live attenuated canine adenovirus type 2 expressing H3N2 CIV hemagglutinin (rCAV2-HA); and 3) an inactivated H3N2 CIV (A/canine/Guangdong/01/2006 (H3N2)). Mice received an initial intramuscular immunization that followed two booster injections at 2 and 4 weeks post-vaccination (wpv). The splenic lymphocytes were collected to assess the immune responses at 6 wpv. The protective efficacy was evaluated by challenging H3N2 CIV after vaccination (at 6 wpv). Our results demonstrated that all three vaccine candidates elicited cytokine and antibody responses in mice. The rCAV2-HA vaccine and the inactivated vaccine generated efficient protective efficacy in mice, whereas limited protection was provided by the pVAX1-HA DNA vaccine. Therefore, both the rCAV2-HA live recombinant virus and the inactivated CIV could be used as potential novel vaccines against H3N2CIV. This study provides guidance for choosing the most appropriate vaccine for the prevention and control of CIV disease.

Novel adenoviruses detected in British mustelids, including a unique Aviadenovirus in the tissues of pine martens (Martes martes).

Several adenoviruses are known to cause severe disease in veterinary species. Recent evidence suggests that canine adenovirus type 1 (CAV-1) persists in the tissues of healthy red foxes (Vulpes vulpes), which may be a source of infection for susceptible species. It was hypothesized that mustelids native to the UK, including pine martens (Martes martes) and Eurasian otters (Lutra lutra), may also be persistently infected with adenoviruses. Based on high-throughput sequencing and additional Sanger sequencing, a novel Aviadenovirus, tentatively named marten adenovirus type 1 (MAdV-1), was detected in pine marten tissues. The detection of an Aviadenovirus in mammalian tissue has not been reported previously. Two mastadenoviruses, tentatively designated marten adenovirus type 2 (MAdV-2) and lutrine adenovirus type 1 (LAdV-1), were also detected in tissues of pine martens and Eurasian otters, respectively. Apparently healthy free-ranging animals may be infected with uncharacterized adenoviruses with possible implications for translocation of wildlife.

Evaluation of a multicomponent vaccine in dogs

The concept of combined viral and bacterial vaccines has been tried in cattle, canine and humans. Use of multicomponent vaccines has numerous advantages over individual vaccine. In this study, apparently healthy 8-9 weeks old 41 puppies were divided into 2 groups. 31 puppies (test group) were vaccinated subcutaneously with a commercially available multicomponent vaccine containing live attenuated strains of Canine Distemper virus, Canine Adenovirus type 2, Canine Parvo virus and Canine Parainfluenza virus and inactivated antigens of Leptospira canicola and Leptospira icterohemorrhagiae. 10 puppies were kept unvaccinated (control). Test group puppies were given a booster after 4 weeks of primary vaccination. Serum samples from both the groups were collected on 4 occasions (0th, 28th, 42nd and 90th day) and were tested for antibody titres against Canine Distemper virus and Canine Adenovirus type 2 by Serum Neutralization test, against Canine Parvovirus and Canine Parainfluenzavirus by Haemagglutination Inhibition test and against Leptospira canicola and L. icterohemorrhagiae by Microscopic Agglutination Test. A significant rise (P 0.5) in antibody titres was observed against all the antigens after vaccination. The control group did not show significant variation in the antibody titres. All puppies vaccinated subcutaneously with this vaccine did not evoke any local/ adverse reactions.

SURVEILLANCE FOR ANTIBODIES AGAINST SIX CANINE VIRUSES IN WILD RACCOONS (PROCYON LOTOR) IN JAPAN.

Raccoons (Procyon lotor) are found worldwide. They are frequently seen in crowded inner cities as well as in forests or wooded areas, often living in proximity to humans and their pets. We examined sera from 100 wild raccoons in Japan for antibodies to six canine viruses with veterinary significance to assess their potential as reservoirs. We also aimed to understand the distribution of potentially infected wildlife. We found that 7% of samples were seropositive for canine distemper virus (CDV), 10% for canine parvovirus type 2, 2% for canine adenovirus type 1, 6% for canine adenovirus type 2, and 7% for canine coronavirus. No samples were found to be seropositive for canine parainfluenza virus. Seropositivity rates for canine distemper virus and canine parvovirus type 2 were significantly different between areas, and younger raccoons (<1 yr old) were more frequently seropositive than older raccoons. Because raccoons belong to the suborder Caniformia, similar to dogs (Canis lupus familiaris), our results suggest that they can act as reservoirs for some of these important canine viruses and might be involved in viral transmission. Further study should include isolation and analysis of canine viruses in wild raccoons from a wider area.

Novel sequence variants of viral hexon and fibre genes in two dogs with canine adenovirus type 1-associated disease

There is little information on sequence variation of canine adenovirus type 1 (CAdV-1), the aetiological agent of infectious canine hepatitis (ICH). This study reports hexon and fibre gene sequence variants of CAdV-1 in a dog with systemic ICH and a dog with the ocular form of the disease (‘blue eye’) in Northern Italy in 2013. One of the sequence variants matched a CAdV-1 fox sequence previously detected in Italy.

Genome Sequence of Canine Adenovirus Type 1 Isolated from a Wolf (Canislupus) in Southern Italy.

ABSTRACTCanine adenovirus type 1 (CAdV-1), a DNA virus of the family Adenoviridae, causes infectious canine hepatitis, a highly contagious disease primarily affecting canids. In this report, we describe the isolation and whole-genome sequence of a CAdV-1 isolate from the liver of a free-ranging wolf (Canis lupus).

A Novel Recombinant Canine Adenovirus Type 1 Detected from Acute Lethal Cases of Infectious Canine Hepatitis

In this study, canine adenoviruses (CAdVs) from two acute fatal cases of infectious canine hepatitis (ICH) were analyzed using molecular detection and sequencing of the pVIII, E3, and fiber protein genes. Pathological findings in affected dogs were typical for CAdV-1 associated disease, characterized by severe centrilobular to panlobular necrohemorrhagic hepatitis and the development of disseminated intravascular coagulation in the terminal stages of disease. Comparison of partial genome sequences revealed that although these newly detected viruses mainly had CAdV-1 genome characteristics, their pVIII gene was more similar to that of CAdV-2. This likely suggests that a recombination has occurred between CAdV-1 and CAdV-2, which possibly explains the cause of vaccine failure or increased virulence of the virus in the observed ICH cases.

European red foxes (Vulpes vulpes) as a possible reservoir for canine adenovirus type 1

European red foxes (Vulpes vulpes) as a possible reservoir for canine adenovirus type 1

Serological and molecular epidemiology of canine adenovirus type 1 in red foxes (Vulpes vulpes) in the United Kingdom.

Canine adenovirus type 1 (CAV-1) causes infectious canine hepatitis (ICH), a frequently fatal disease which primarily affects canids. In this study, serology (ELISA) and molecular techniques (PCR/qPCR) were utilised to investigate the exposure of free-ranging red foxes (Vulpes vulpes) to CAV-1 in the United Kingdom (UK) and to examine their role as a wildlife reservoir of infection for susceptible species. The role of canine adenovirus type 2 (CAV-2), primarily a respiratory pathogen, was also explored. In foxes with no evidence of ICH on post-mortem examination, 29 of 154 (18.8%) red foxes had inapparent infections with CAV-1, as detected by a nested PCR, in a range of samples, including liver, kidney, spleen, brain, and lung. CAV-1 was detected in the urine of three red foxes with inapparent infections. It was estimated that 302 of 469 (64.4%) red foxes were seropositive for canine adenovirus (CAV) by ELISA. CAV-2 was not detected by PCR in any red foxes examined. Additional sequence data were obtained from CAV-1 positive samples, revealing regional variations in CAV-1 sequences. It is concluded that CAV-1 is endemic in free-ranging red foxes in the UK and that many foxes have inapparent infections in a range of tissues.