Emerging animal viruses: real threats or simple bystanders?

The list of animal viruses has been frequently added of new members raising permanent concerns to virologists and veterinarians. The pathogenic potential and association with disease have been clearly demonstrated for some, but not for all of these emerging viruses. This review describes recent discoveries of animal viruses and their potential relevance for veterinary practice. Dogs were considered refractory to influenza viruses until 2004, when an influenza A virus subtype H3N8 was transmitted from horses and produced severe respiratory disease in racing greyhounds in Florida/USA. The novel virus, named canine influenza virus (CIV), is considered now a separate virus lineage and has spread among urban canine population in the USA. A new pestivirus (Flaviviridae), tentatively called HoBi-like pestivirus, was identified in 2004 in commercial fetal bovine serum from Brazil. Hobi-like viruses are genetically and antigenically related to bovine viral diarrhea virus (BVDV) and induce similar clinical manifestations. These novel viruses seem to be widespread in Brazilian herds and have also been detected in Southeast Asia and Europe. In 2011, a novel mosquito-borne orthobunyavirus, named Schmallenberg virus (SBV), was associated with fever, drop in milk production, abortion and newborn malformation in cattle and sheep in Germany. Subsequently, the virus disseminated over several European countries and currently represents a real treat for animal health. The origin of SBV is still a matter of debate but it may be a reassortant from previous known bunyaviruses Shamonda and Satuperi. Hepatitis E virus (HEV, family Hepeviridae) is a long known agent of human acute hepatitis and in 1997 was first identified in pigs. Current data indicates that swine HEV is spread worldwide, mainly associated with subclinical infection. Two of the four HEV genotypes are zoonotic and may be transmitted between swine and human by contaminated water and undercooked pork meat. The current distribution and impact of HEV infection in swine production are largely unknown. Avian gyrovirus type 2 (AGV2) is a newly described Gyrovirus, family Circoviridae, which was unexpectedly found in sera of poultry suspected to be infected with chicken anemia virus (CAV). AGV2 is closely related to CAV but displays sufficient genomic differences to be classified as a distinct species. AGV2 seems to be distributed in Brazil and also in other countries but its pathogenic role for chickens is still under investigation. Finally, the long time and intensive search for animal relatives of human hepatitis C virus (HCV) has led to the identification of novel hepaciviruses in dogs (canine hepacivirus [CHV]), horses (non-primate hepaciviruses [NPHV] or Theiler's disease associated virus [TDAV]) and rodents. For these, a clear and definitive association with disease is still lacking and only time and investigation will tell whether they are real disease agents or simple spectators.

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The enigma of the apparent disappearance of Eurasian highly pathogenic H5 clade 2.3.4.4 influenza A viruses in North American waterfowl

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608853113 ◽

2016 ◽

Vol 113 (32) ◽

pp. 9033-9038 ◽

Cited By ~ 37

Author(s):

Scott Krauss ◽

David E. Stallknecht ◽

Richard D. Slemons ◽

Andrew S. Bowman ◽

Rebecca L. Poulson ◽

...

Keyword(s):

United States ◽

North America ◽

North American ◽

Influenza A ◽

Wild Bird ◽

Animal Health ◽

The United States ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Highly Pathogenic

One of the major unresolved questions in influenza A virus (IAV) ecology is exemplified by the apparent disappearance of highly pathogenic (HP) H5N1, H5N2, and H5N8 (H5Nx) viruses containing the Eurasian hemagglutinin 2.3.4.4 clade from wild bird populations in North America. The introduction of Eurasian lineage HP H5 clade 2.3.4.4 H5N8 IAV and subsequent reassortment with low-pathogenic H?N2 and H?N1 North American wild bird-origin IAVs in late 2014 resulted in widespread HP H5Nx IAV infections and outbreaks in poultry and wild birds across two-thirds of North America starting in November 2014 and continuing through June 2015. Although the stamping out strategies adopted by the poultry industry and animal health authorities in Canada and the United States—which included culling, quarantining, increased biosecurity, and abstention from vaccine use—were successful in eradicating the HP H5Nx viruses from poultry, these activities do not explain the apparent disappearance of these viruses from migratory waterfowl. Here we examine current and historical aquatic bird IAV surveillance and outbreaks of HP H5Nx in poultry in the United States and Canada, providing additional evidence of unresolved mechanisms that restrict the emergence and perpetuation of HP avian influenza viruses in these natural reservoirs.

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Emerging Viruses Are Inactivated by Pasteurization.

Blood ◽

10.1182/blood.v104.11.4111.4111 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4111-4111

Author(s):

Albrecht Groener ◽

Wolfram Schäfer ◽

Thomas Nowak

Keyword(s):

Avian Influenza ◽

Influenza Viruses ◽

Virus Infectivity ◽

Suitable Model ◽

Sars Coronavirus ◽

Emerging Viruses ◽

Avian Influenza Viruses ◽

Diarrhea Virus ◽

Short Period ◽

Model Virus

Abstract Emerging zoonotic viruses as West Nile virus (WNV), SARS coronavirus, and avian influenza viruses have raised concern about their potential presence in blood/plasma. However, so far only WNV has been demonstrated to be transmitted via blood transfusion. Pasteurization (heat treatment in aqueous stabilized solution at 60°C for 10 hours) is an integral part of the manufacturing process of ZLB Behring’s coagulation factor concentrates such as Haemate P / Humate-P, Monoclate-P, Beriate P, and Berinin P as well as other plasma-derived medicinal products. Therefore, the virus inactivation capacity of this manufacturing step was evaluated utilizing these emerging viruses or appropriate model viruses in virus spiking studies in order to assess the safety of plasma derivatives. The studies demonstrated that WNV was inactivated very effectively by pasteurization in different plasma derivatives resulting in an inactivation factor of more than 7 log10 and that BVDV (bovine viral diarrhea virus, as WNV a member of the family Flaviviridae) is a suitable model virus for WNV. Furthermore, coronaviruses and influenza viruses, of both avian and human origin, were highly susceptible to inactivation by pasteurization resulting in complete inactivation of virus infectivity within a short period of time. In addition, feline calicivirus, a model virus for hepatitis E virus (HEV), was inactivated very effectively within a short period of time. We demonstrate that pasteurization is an effective method to inactivate the emerging viruses WNV, SARS coronavirus, and avian influenza viruses as well as HEV below detection limit of a sensitive cell culture infectivity assay resulting in a safe plasma derivative.

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A Synthetic Modified Live Chimeric Marker Vaccine against BVDV-1 and BVDV-2

Vaccines ◽

10.3390/vaccines8040577 ◽

2020 ◽

Vol 8 (4) ◽

pp. 577

Author(s):

Susanne Koethe ◽

Patricia König ◽

Kerstin Wernike ◽

Florian Pfaff ◽

Jana Schulz ◽

...

Keyword(s):

Vaccine Candidate ◽

Animal Health ◽

Distinct Species ◽

Vaccine Virus ◽

Type I ◽

Virus Infections ◽

Elisa System ◽

Diarrhea Virus ◽

Marker Vaccine ◽

High Level

Bovine viral diarrhea virus (BVDV), a pestivirus which exists in the two distinct species BVDV-1 (syn. Pestivirus A) and BVDV-2 (syn. Pestivirus B), is the causative agent of one of the most widespread and economically important virus infections in cattle. For economic as well as for animal health reasons, an increasing number of national BVDV control programs were recently implemented. The main focus lies on the detection and removal of persistently infected cattle. The application of efficient marker or DIVA (differentiation of infected from vaccinated animals) vaccines would be beneficial for the eradication success in regions with a high BVDV prevalence to prevent fetal infection and it would allow serological monitoring of the BVDV status also in vaccinated farms. Therefore, a marker vaccine based on the cytopathic (cp) BVDV-1b strain CP7 was constructed as a synthetic backbone (BVDV-1b_synCP7). For serological discrimination of vaccinated from infected animals, the viral protein Erns was substituted by the heterologous Erns of Bungowannah virus (BuPV, species Pestivirus F). In addition, the vaccines were attenuated by a deletion within the type I interferon inhibitor Npro protein encoding sequence. The BVDV-2 vaccine candidate is based on the genetic sequence of the glycoproteins E1 and E2 of BVDV-2 strain CS8644 (CS), which were introduced into the backbone of BVDV-1b_synCP7_ΔNpro_Erns Bungo in substitution of the homologous glycoproteins. Vaccine virus recovery resulted in infectious cytopathic virus chimera that grew to titers of up to 106 TCID50/mL. Both synthetic chimera BVDV-1b_synCP7_ΔNpro_Erns Bungo and BVDV-1b_synCP7_ΔNpro_Erns Bungo_E1E2 BVDV-2 CS were avirulent in cattle, provided a high level of protection in immunization and challenge experiments against both BVDV species and allowed differentiation of infected from vaccinated cattle. Our study presents the first report on an efficient BVDV-1 and -2 modified live marker vaccine candidate and the accompanying commercially available serological marker ELISA system.

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A29 Genetic heterogeneity of influenza A (H3N2) viruses in the United Kingdom, 2016–8

Virus Evolution ◽

10.1093/ve/vez002.028 ◽

2019 ◽

Vol 5 (Supplement_1) ◽

Author(s):

M Galiano ◽

S Miah ◽

O Akinbami ◽

S Gonzalez Gonoggia ◽

J Ellis ◽

...

Keyword(s):

Amino Acid ◽

Genetic Heterogeneity ◽

Influenza A ◽

Evolutionary Dynamics ◽

Sequence Data ◽

Influenza Viruses ◽

Clinical Samples ◽

Gene Trees ◽

Emerging Viruses ◽

The Uk

Abstract For the last four influenza seasons in the UK, genetic characterization of seasonal influenza viruses has shifted from single hemagglutinin (HA) and neuraminidase (NA) genes to whole genome (WG) analysis, allowing for better insight into the evolutionary dynamics of this virus. Sequences (WG or HA/NA) were obtained from >900A (H3N2) viruses sampled in the UK during influenza seasons 2016/7 and 2017/8 and the inter-seasonal period. Viral RNA was extracted from clinical samples and amplified using a multi-segment RT-PCR. Amplicons were sequenced using Nextera library preparation for Illumina MiSeq sequencing. Sequence data ????were processed using BAM-SAM tools and PHE in-house scripts. Phylogenetic analysis of the HA gene indicates that they belong to genetic group 3C.2a, which has circulated since 2014. Season 2016/7 was characterized by the emergence of cluster 3C.2a.1; further genetic heterogeneity was seen with 6 new subclusters within 3C.2a and 3C.2a.1, with predominance of those characterized by amino acid changes N121K and S144K (3C.2a) and N121K, N171K, I406K, G484E (3C.2a.1). The NA genes clustered with a similar topology to the HA. Season 2017/8 was characterized by persistence of some clades from previous season with further diversification. Three of the 3C.2a clusters continued to circulate, with predominance of clade showing T131K, R142K, and R261Q (clade 3C.2a.2). The majority of HA sequences in 3C.2a1 fall into a new subcluster which has become predominant within this subgroup, with amino acid changes E62G, K92R, and T135K (3C.2a.1b). The topology of NA and internal gene trees showed evidence of reassortment events occurring at some point between the two seasons, with group 3C.2a2 acquiring NA and some internal genes from 3C.2a1 lineage viruses. The predominance of this group during 2017–8 might be due to fitness advantage related to the new genetic constellation. Emerging viruses from group 3C.3a also have acquired genes from lineage 3C.2a1, which could be the reason for their increased frequency to 20 per cent by the end of season 2017–8. Molecular epidemiology indicates emerging genetic diversity in A(H3N2) viruses during the period of study, leading to co-circulation of variants. The frequency of circulating HA genetic groups was quite variable, with rapidly changing patterns of predominance. Evidence of reassortment events was observed which could be responsible for the rise and predominance of some clades, and might predict the emergence of other variants.

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Sequential Immunization with Universal Live Attenuated Influenza Vaccine Candidates Protects Ferrets against a High-Dose Heterologous Virus Challenge

Vaccines ◽

10.3390/vaccines7030061 ◽

2019 ◽

Vol 7 (3) ◽

pp. 61 ◽

Cited By ~ 6

Author(s):

Irina Isakova-Sivak ◽

Victoria Matyushenko ◽

Tatiana Kotomina ◽

Irina Kiseleva ◽

Elena Krutikova ◽

...

Keyword(s):

Influenza A ◽

Clinical Symptoms ◽

Protective Efficacy ◽

Clinical Signs ◽

Clinical Manifestations ◽

Influenza Viruses ◽

Influenza Vaccines ◽

Control Group ◽

High Dose ◽

T Cell Epitopes

The development of universal influenza vaccines has been a priority for more than 20 years. We conducted a preclinical study in ferrets of two sets of live attenuated influenza vaccines (LAIVs) expressing chimeric hemagglutinin (cHA). These vaccines contained the HA stalk domain from H1N1pdm09 virus but had antigenically unrelated globular head domains from avian influenza viruses H5N1, H8N4 and H9N2. The viral nucleoproteins (NPs) in the two sets of universal LAIV candidates were from different sources: one LAIV set contained NP from A/Leningrad/17 master donor virus (MDV), while in the other set this gene was from wild-type (WT) H1N1pdm09 virus, in order to better match the CD8 T-cell epitopes of currently circulating influenza A viruses. To avoid any difference in protective effect of the various anti-neuraminidase (NA) antibodies, all LAIVs were engineered to contain the NA gene of Len/17 MDV. Naïve ferrets were sequentially immunized with three doses of (i) classical LAIVs containing non-chimeric HA and NP from MDV (LAIVs (NP-MDV)); (ii) cHA-based LAIVs containing NP from MDV (cHA LAIVs (NP-MDV)); and (iii) cHA-based LAIVs containing NP from H1N1pdm09 virus (cHA LAIVs (NP-WT)). All vaccination regimens were safe, producing no significant increase in body temperature or weight loss, in comparison with the placebo group. The two groups of cHA-based vaccines induced a broadly reactive HA stalk-directed antibody, while classical LAIVs did not. A high-dose challenge with H1N1pdm09 virus induced significant pathology in the control, non-immunized ferrets, including high virus titers in respiratory tissues, clinical signs of disease and histopathological changes in nasal turbinates and lung tissues. All three vaccination regimens protected animals from clinical manifestations of disease: immunized ferrets did not lose weight or show clinical symptoms, and their fever was significantly lower than in the control group. Further analysis of virological and pathological data revealed the following hierarchy in the cross-protective efficacy of the vaccines: cHA LAIVs (NP-WT) > cHA LAIVs (NP-MDV) > LAIVs (NP-MDV). This ferret study showed that prototype universal cHA-based LAIVs are highly promising candidates for further clinical development.

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Influenza: A current medical problem

Medicinski pregled ◽

10.2298/mpns0708351b ◽

2007 ◽

Vol 60 (7-8) ◽

pp. 351-356

Author(s):

Ivanko Bojic ◽

Olga Dulovic ◽

Eleonora Gvozdenovic ◽

Svetlana Minic

Keyword(s):

Influenza Virus ◽

Human Population ◽

Influenza A ◽

Respiratory Infections ◽

Clinical Manifestations ◽

Supportive Therapy ◽

Type A ◽

Influenza Viruses ◽

Laboratory Findings ◽

Important Place

Introduction. Acute respiratory infections are the most common infections in the human population. Among them, virus infections, especially those caused by influenza viruses, have an important place. Type A influenza. Type A influenza virus caused three epidemics during the last century. A high percetage of deceased in pandemics of 1918, and 1919 were young, healthy persons, with many of the deaths due to an unusually severe, hemorrhagic pneumonia. At the end of 2003, and the beginning of 2004, an epidemic emerged in South East Asia of poultry influenza caused by animal (avian) virus. Later it spread to the human population, with a high death rate of 73% and with a possibility of interhuman transmission. This review article provides an overview of the clinical manifestations, laboratory findings and chest radiographs. Apart from the symptomatic and supportive therapy, there are antiviral drugs and corticosteriods. Conclusion. The use of vaccine containing subtypes of virus hemagglutinins and neuraminidase from an influenza virus currently infecting the population has a great importance. .

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Long-Term Consequence of Non-neurotropic H3N2 Influenza A Virus Infection for the Progression of Alzheimer’s Disease Symptoms

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.643650 ◽

2021 ◽

Vol 15 ◽

Author(s):

Shirin Hosseini ◽

Kristin Michaelsen-Preusse ◽

Klaus Schughart ◽

Martin Korte

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Influenza A Virus ◽

Influenza A ◽

Animal Health ◽

Amyloid Β ◽

Influenza Viruses ◽

Spine Density

Influenza viruses until today are a leading cause of worldwide severe pandemics and represent a major threat to human and animal health. Although the primary target of influenza viruses is the lung, infection may manifest with acute and even chronic neurological complications (e.g., status epilepticus, encephalopathies, and encephalitis) potentially increasing the long-term risk for neurodegenerative diseases. We previously described that a peripheral influenza A virus (IAV) infection caused by non-neurotropic H3N2 (maHK68) variant leads to long-term neuroinflammation and synapse loss together with impaired memory formation in young adult mice. Processes of neuroinflammation have been associated with neurodegenerative diseases such as Alzheimer’s disease (AD) and prolonged or excessive innate immune responses are considered a risk factor for AD. Here, the role of purely peripheral IAV infection for the development and progression of AD in a transgenic mouse model (APP/PS1) was investigated. At 2 months of age, mice were infected with H3N2 IAV and the detailed analysis of microglia morphology revealed neuroinflammation in the hippocampus already of 6 months old non-infected APP/PS1 mice together with impaired spatial learning, however, microglia activation, amyloid-β plaques load and cognitive impairments were even more pronounced in APP/PS1 mice upon H3N2 infection. Moreover, CA1 hippocampal dendritic spine density was reduced even at 120 dpi compared to wild-type and also to non-infected APP/PS1 mice, whereas neuronal cells number was not altered. These findings demonstrate that non-neurotropic H3N2 IAV infection as a peripheral immune stimulation may exacerbate AD symptoms possibly by triggering microglial hyperactivation.

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Screening of Eurasian Tundra Reindeer for Viral Sequences by Next-Generation Sequencing

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18126561 ◽

2021 ◽

Vol 18 (12) ◽

pp. 6561

Author(s):

Javier Sánchez Romano ◽

Anna Omazic ◽

Mikael Leijon ◽

Åsa Hagström ◽

Morten Tryland ◽

...

Keyword(s):

Next Generation Sequencing ◽

Roe Deer ◽

Animal Health ◽

Farm Animals ◽

The Arctic ◽

Sequencing Analysis ◽

Next Generation ◽

Emerging Viruses ◽

Diarrhea Virus ◽

Generation Sequencing

Reindeer husbandry is essential for the livelihood and culture of indigenous people in the Arctic. Parts of the herding areas are also used as pastures for farm animals, facilitating potential transmission of viruses between species. Following the Covid-19 pandemic, viruses circulating in the wild are receiving increased attention, since they might pose a potential threat to human health. Climate change will influence the prevalence of infectious diseases of both humans and animals. The aim of this study was to detect known and previously unknown viruses in Eurasian tundra reindeer. In total, 623 nasal and 477 rectal swab samples were collected from reindeer herds in Fennoscandia, Iceland, and Eastern Russia during 2016–2019. Next-generation sequencing analysis and BLAST-homology searches indicated the presence of viruses of domesticated and wild animals, such as bovine viral diarrhea virus, bovine papillomavirus, alcephaline herpesvirus 1 and 2, deer mastadenovirus B, bovine rotavirus, and roe deer picobirnavirus. Several viral species previously found in reindeer and some novel species were detected, although the clinical relevance of these viruses in reindeer is largely unknown. These results indicate that it should be possible to find emerging viruses of relevance for both human and animal health using reindeer as a sentinel species.

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Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine

10.1101/2020.05.29.123828 ◽

2020 ◽

Author(s):

Michael A. Zeller ◽

Jennifer Chang ◽

Amy L. Vincent ◽

Phillip C. Gauger ◽

Tavis K. Anderson

Keyword(s):

Genetic Diversity ◽

Influenza A Virus ◽

Influenza A ◽

Animal Health ◽

Rapid Evolution ◽

Influenza Viruses ◽

Antigenic Drift ◽

Control Programs ◽

Essential Surface ◽

Gene Reassortment

AbstractThe neuraminidase (NA) and hemagglutinin (HA) of influenza A virus (IAV) are essential surface glycoproteins. In this study, the evolution of subtype N2 NA paired with H1 and H3 subtype HA in swine was evaluated to understand if genetic diversity of HA and NA were linked. Using time-scaled Bayesian phylodynamic analyses, the relationships of paired swine N2 with H1 or H3 from 2009 to 2018 were evaluated. These data demonstrated increased relative genetic diversity within the major N2 clades circulating in swine (N2.1998 between 2014-2017 and N2.2002 between 2010-2016). Relative genetic diversity of NA-HA pairs (e.g., N2.1998B/ H1.Delta1B) were correlated, suggesting intergene epistasis. Preferential pairing was observed among specific NA and HA genetic clades and this was associated with gene reassortment between cocirculating influenza A strains. Using the phylogenetic topology of inferred N2 trees, the expansion of genetic diversity in the NA gene was quantified and increases in diversity were observed subsequent to NA-HA reassortment events. The rate of evolution among NA-N2 clades and HA-H1 and HA-H3 clades were similar. The frequent regional movement of pigs and their influenza viruses is a possible explanation driving this pattern of drift, reassortment, and rapid evolution. Bayesian phylodynamic analyses demonstrated strong spatial patterns in N2 genetic diversity, and that frequent interstate movement of N2 clades homogenized diversity. The reassortment and evolution of NA and its influence on HA evolution may affect antigenic drift, impacting vaccine control programs and animal health.

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Global patterns of avian influenza A (H7): virus evolution and zoonotic threats

FEMS Microbiology Reviews ◽

10.1093/femsre/fuz019 ◽

2019 ◽

Cited By ~ 1

Author(s):

Mahmoud M Naguib ◽

Josanne H Verhagen ◽

Ahmed Mostafa ◽

Michelle Wille ◽

Ruiyun Li ◽

...

Keyword(s):

Avian Influenza ◽

Influenza A ◽

Negative Impact ◽

Sequence Data ◽

Influenza Viruses ◽

Emerging Viruses ◽

Highly Pathogenic ◽

Zoonotic Infections ◽

Global Patterns ◽

Human Infections

ABSTRACT Avian influenza viruses (AIVs) continue to impose a negative impact on animal and human health worldwide. In particular, the emergence of highly pathogenic AIV H5 and, more recently, the emergence of low pathogenic AIV H7N9 have led to enormous socioeconomical losses in the poultry industry and resulted in fatal human infections. While H5N1 remains infamous, the number of zoonotic infections with H7N9 has far surpassed those attributed to H5. Despite the clear public health concerns posed by AIV H7, it is unclear why specifically this virus subtype became endemic in poultry and emerged in humans. In this review, we bring together data on global patterns of H7 circulation, evolution and emergence in humans. Specifically, we discuss data from the wild bird reservoir, expansion and epidemiology in poultry, significant increase in their zoonotic potential since 2013 and genesis of highly pathogenic H7. In addition, we analysed available sequence data from an evolutionary perspective, demonstrating patterns of introductions into distinct geographic regions and reassortment dynamics. The integration of all aspects is crucial in the optimisation of surveillance efforts in wild birds, poultry and humans, and we emphasise the need for a One Health approach in controlling emerging viruses such as AIV H7.

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