key: cord-0730638-k3hy2ewx
authors: Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Chen, Honglin; Yuen, Kwok-Yung
title: Cross-species transmission and emergence of novel viruses from birds
date: 2015-01-31
journal: Curr Opin Virol
DOI: 10.1016/j.coviro.2015.01.006
sha: be33a593fc84e85ffc3cad82dbe2e65c26539778
doc_id: 730638
cord_uid: k3hy2ewx

Birds, the only living member of the Dinosauria clade, are flying warm-blooded vertebrates displaying high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system. Birds provide the natural reservoir for numerous viral species and therefore gene source for evolution, emergence and dissemination of novel viruses. The intrusions of human into natural habitats of wild birds, the domestication of wild birds as pets or racing birds, and the increasing poultry consumption by human have facilitated avian viruses to cross species barriers to cause zoonosis. Recently, a novel adenovirus was exclusively found in birds causing an outbreak of Chlamydophila psittaci infection among birds and humans. Instead of being the primary cause of an outbreak by jumping directly from bird to human, a novel avian virus can be an augmenter of another zoonotic agent causing the outbreak. A comprehensive avian virome will improve our understanding of birds’ evolutionary dynamics.

Jasper Fuk-Woo Chan 1 , Kelvin Kai-Wang To 1 , Honglin Chen and Kwok-Yung Yuen Birds, the only living member of the Dinosauria clade, are flying warm-blooded vertebrates displaying high species biodiversity, roosting and migratory behavior, and a unique adaptive immune system. Birds provide the natural reservoir for numerous viral species and therefore gene source for evolution, emergence and dissemination of novel viruses. The intrusions of human into natural habitats of wild birds, the domestication of wild birds as pets or racing birds, and the increasing poultry consumption by human have facilitated avian viruses to cross species barriers to cause zoonosis. Recently, a novel adenovirus was exclusively found in birds causing an outbreak of Chlamydophila psittaci infection among birds and humans. Instead of being the primary cause of an outbreak by jumping directly from bird to human, a novel avian virus can be an augmenter of another zoonotic agent causing the outbreak. A comprehensive avian virome will improve our understanding of birds' evolutionary dynamics.

Birds are flying warm-blooded vertebrates of the class Aves. They are the most highly biodiversified tetrapods with about 10,000 species. The evolution of birds from bipedal carnivorous dinosaurs through sustained miniaturization and anatomical innovation over approximately 160 million years is one of the most compelling examples of macroevolution [1 ] . Modern-day birds are believed to be the only living members of the Dinosauria clade. Their unparalleled biodiversity and length of evolution among animals have provided abundant opportunities for virus acquisition from various sources. Their unique adaptive immune system allows asymptomatic infection and virus co-evolution to occur [2 ] . Their global distribution, annual long distance migrations, and habitual roosting in environments shared by other animals further enhance the mixing and dissemination of viruses to and from other species.

These biological, immunological, and ecological characteristics have given birds distinctive roles in the emergence of novel viruses and their cross-species transmission [2 ]. Birds may act as a vehicle for vector dissemination, an amplifying host in bird-vector-bird cycles, or the gene source of emerging viruses in cross-species virus transmission ( Figure 1) Sixteen of 18 hemagglutinin (HA) subtypes and nine of 11 neuraminidase (NA) subtypes of influenza viruses can be found in birds, especially waterfowl and shorebirds [2 ] . Out of a possible 144 HA and NA combinations, 112 were identified in wild birds, including 49 that were also found in domestic birds [14] . Since most of these avian influenza viruses are of low pathogenicity in birds, infected migratory birds can carry different influenza virus subtypes for long distances. Mixed infection is also commonly identified [15] . Therefore, waterfowls remain the most important source of genetic diversity for influenza viruses.

Although wild birds harbor the most diverse subtypes of influenza viruses, reassortment and amplification events of avian influenza viruses affecting humans most likely occur in live poultry markets (LPM) where there are high densities of poultries [16, 17 ] . Surveillance studies showed that avian influenza viruses were found more commonly in poultry samples collected in LPM than in wild bird samples or backyard poultry samples [18] . Next-generation sequencing showed that mixed infection of different subtypes is common among poultries in LPM [19] . Phylogenetic studies suggested that A(H7N9) and A(H10N8) viruses are reassortants with internal genes originating from A(H9N2) viruses that are circulating in poultries [16,17 ,20] . Unlike A(H5N1) virus which is highly pathogenic for poultries, A(H7N9) and A(H10N8) viruses tend to cause asymptomatic avian infections, and therefore widespread circulation of A(H7N9) and A(H10N8) viruses among poultries were not recognized until human cases appeared.

Only few avian influenza viruses can be transmitted directly from birds to humans. These avian influenza viruses are usually amplified and mixed in the poultry population before transmission from poultries to humans. For example, both A(H7N9) and A(H10N8) viruses affecting humans carry internal genes originating from A(H9N2) isolated from poultries [20] . Direct contact between humans and infected poultries therefore poses a high risk of transmission. Epidemiological studies suggested that humans without direct contact with infected poultries can also be infected via contacting the contaminated environment in live poultries markets [21] . Older age and presence of underlying diseases are risk factors for A(H7N9) virus infection, but most patients with A(H5N1) virus infection do not have these risk factors [22] . Beside epidemiological and host factors, many studies have tried to elucidate the virological characteristics allowing a particular virus subtype to cause human disease. Traditionally, the sialic acid receptor preference of the viral surface glycoprotein HA has been the focus of attention [5 ,23] . Avian influenza viruses and human seasonal influenza viruses preferentially bind to a2,3linked sialic acid receptor (a2,3 SA) and a2,6-linked sialic acid receptor (a2,6 SA), respectively. Some human A(H5N1) virus isolates had increased affinity to a2,6 SA [24] . The distribution of receptors also differs between humans and birds. In humans, the nasal mucosa, paranasal sinuses, pharynx, trachea and bronchi are mainly lined by a2,6 SA, while the non-ciliated cuboidal bronchiolar cells and type II pneumocytes in the alveoli express a2,3 SA [25] . In chickens and quails, a2,3 SA and a2,6 SA are found on the epithelial cells of both the intestine and respiratory tract. In ducks, only a2,3 SA can be found in the intestine, while a2,3 SA are much more abundant than a2,6 SA in the trachea [ Adaptations that affect viral polymerase function have been extensively studied and several markers which enhanced virus replication in mammals have been identified in the basic polymerase 2 (PB2), basic polymerase 1 (PB1), acid polymerase (PA), nucleoprotein (NP) and nuclear export protein (NEP) [29] . One of the most important substitution is the PB2 E627K, which has been associated with enhanced viral replication at the temperature of the human upper respiratory tract and were identified in many human isolates of A(H7N9) and A(H10N8) viruses [10 ,27,30]. PB2 K562R substitution, which is present in some A(H7N9) strains and 80% of A(H5N1) strains, also increase viral polymerase activity [31] . Other important mutations of PB2 include D701N, Q591K, and T271A [29] . Recent findings appear to favor a hypothesis that compatibility between subunits of ribonucleoprotein (RNP) and NEP which facilitate viral genome trafficking from nucleus to cytoplasm for virus packaging at late stage of infection determine the fitness of viral genome for host adaptation [32] .

Several groups have investigated mammalian adaptation of avian influenza viruses by generating mutant avian influenza viruses capable of non-contact transmission between ferrets. Studies on A(H5N1) viruses generated by serial passage in ferrets showed that mutations affecting receptor binding, fusion of viral and host cell membrane, and polymerase activity are important for transmission via the non-contact route [33, 34] . A study using influenza viruses generated with gene segments originating from circulating avian influenza viruses and the 1918 pandemic A(H1N1) virus showed that substitutions in the HA, PB2 and PA are important for virulence and efficient transmission in ferrets [35] .

In addition to the avian influenza viruses subtypes H5, H7, H9 and H10 that are transmitted directly from birds or the contaminated environment to humans, several pandemic influenza viruses also carry gene segments originating from birds. These gene segments from avian viruses reassort with those from circulating human or swine influenza viruses. The PB1, HA and NA of the 1957 A(H2N2) and the PB1 and HA of the 1968 A(H3N2) originated from avian influenza viruses [23] . For the 1918 pandemic A(H1N1) virus, the timing of the introduction of the genes from avian influenza viruses is controversial. However, a recent phylogenomic study showed that the internal genes of the 1918 pandemic A(H1N1) virus originated from the western hemisphere avian influenza virus lineage [36] . Therefore, avian influenza viruses remain to be an important gene source for future pandemic influenza viruses, and continued surveillance among wild birds and poultries is necessary for better understanding of the virus origin in future pandemics. [37] .

Historically, the significance of newly identified avian viruses has mainly been determined by the viral pathogenicity in causing disease in humans or birds directly. Recently, the novel concept of 'pathogen augmentation' was introduced and brought insights into the significance of avian viruses in cross-species transmission of pathogens. A novel adenovirus was detected in Mealy Parrots during an outbreak of avian chlamydiosis and human psittacosis amongst epidemiologically linked workers in an animal detention center in Hong Kong [38 ] . This novel psittacine adenovirus was detected only in the lung, kidney, liver, spleen and cloacal swabs of birds with Chlamydophila psittaci but not in other healthy birds. Moreover, the bacterial load of C. psittaci was higher in adenovirus-infected birds with higher viral load. The adenovirus likely caused immunosuppression of the infected birds which allowed C. psittaci to multiply to high levels with subsequent transmission to humans. These findings demonstrated that infection of birds by an emerging novel virus could lead to an outbreak of reemerging infections such as C. psittaci infection among birds and epidemiologically linked humans. Instead of being the primary cause of the outbreak by jumping directly from bird to human, the novel avian virus acted as an augmenter of another zoonotic agent causing the outbreak. This concept of 'pathogen augmentation' in birds is analogous to the enhanced epidemiological dissemination of Mycobacterium tuberculosis in patients with human immunodeficiency virus infection. It is different from human infection by flaviviruses which are amplified in birds in bird-mosquito-bird cycles. Thus, an unusual outbreak of zoonotic diseases in human may warrant further investigations of the animal source to identify the possible underlying viral infection in epidemiologically linked birds.

In the recent two years, we have witnessed an explosion in avian virus discovery through the application of stateof-the art molecular diagnostic tools. The emerging avian influenza A(H7N9) virus reminds the global health community of the pandemic potential of avian viruses that are capable of crossing species barriers. Continuous, systematic, and global bird surveillance programs are important for the identification of other avian viruses with zoonotic potential. Molecular studies are important in identifying the appropriate adaptive mutations for cross-species transmission or virulent mutants of veterinary significance. The novel concept of 'pathogen augmentation' demonstrated in a recent outbreak of C. psittasi infection associated with a new avian adenovirus highlights the importance of investigating for an underlying viral infection in epidemiologically linked avian source associated with outbreaks of re-emerging zoonoses in human. 

Centre for Health Protection: Avian influenza report

Sampling strategies and biodiversity of influenza a subtypes in wild birds

Serological evidence of H7, H5 and H9 avian influenza virus co-infection among herons in a city park in Jiangxi

Dynamic reassortments and genetic heterogeneity of the human-infecting influenza A (H7N9) virus

Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome

The first study to demonstrate the epidemiological and phylogenetic link between human cases of avian influenza A/H7N9 and infected wet market poultry

Investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza A(H10N8) in Nanchang City

Influenza H7N9 and H9N2 viruses: coexistence in poultry linked to human H7N9 infection and genome characteristics

Poultry carrying H9N2 act as incubators for novel human avian influenza viruses

Epidemiology of human infections with avian influenza A(H7N9) virus in China

Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratoryconfirmed cases

Pandemic threat posed by avian influenza A viruses

Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt

Avian flu: influenza virus receptors in the human airway

Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier

Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong

The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza A virus replication

Emerging roles for the influenza A virus nuclear export protein (NEP)

Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus

Receptor binding by a ferret-transmissible H5 avian influenza virus

Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

A synchronized global sweep of the internal genes of modern avian influenza virus

Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus

A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds

The novel concept of 'pathogen augmentation' in birds is illustrated in an outbreak of avian chalmydiosis and human psittacosis where the Mealy Parrots were co

Avian influenza H7N9/13 and H7N7/13: a comparative virulence study in chickens, pigeons, and ferrets

The World Organisation for Animal Health: Update on highly pathogenic avian influenza in animals (type H5 and H7)

Identification and characterization of a novel adenovirus in the cloacal bursa of gulls

Whole-genome sequences of two turkey adenovirus types reveal the existence of two unknown lineages that merit the establishment of novel species within the genus Aviadenovirus

Full genome analysis of a novel adenovirus from the South Polar skua (Catharacta maccormicki) in Antarctica

A novel adenovirus in Chinstrap penguins (Pygoscelis antarctica) in Antarctica

A novel siadenovirus detected in the kidneys and liver of Gouldian finches (Erythura gouldiae)

Characterization of a novel gyrovirus in human stool and chicken meat

A novel herpesvirus in 3 species of pheasants: mountain peacock pheasant (Polyplectron inopinatum), Malayan peacock pheasant (Polyplectron malacense), and Congo peafowl (Afropavo congensis)

A novel herpesvirus associated with respiratory disease in Bourke's parrots (Neopsephotus bourkii)

A novel papillomavirus in Adelie penguin (Pygoscelis adeliae) faeces sampled at the Cape Crozier colony

The viruses of wild pigeon droppings

Disease screening of three breeding populations of adult exhibition budgerigars (Melopsittacus undulatus) in New Zealand reveals a high prevalence of a novel polyomavirus and avian malaria infection

Phylogenetic and histological variation in avipoxviruses isolated in South Africa

Two different avipoxviruses associated with pox disease in Magellanic penguins (Spheniscus magellanicus) along the Brazilian coast

Novel ssDNA viruses discovered in yellow-crowned parakeet (Cyanoramphus auriceps) nesting material

A novel group of avian astroviruses in wild aquatic birds

Novel coronavirus and astrovirus in Delaware Bay shorebirds

Discovery and genetic characterization of novel caliciviruses in German and Dutch poultry

Identification and survey of a novel avian coronavirus in ducks

Novel avian coronavirus and fulminating disease in guinea fowl

Identification and molecular characterization of a novel flavivirus isolated from Pekin ducklings in China

Identification and molecular characterization of a novel flavivirus isolated from geese in China

Cygnet River virus, a novel orthomyxovirus from ducks

Complete genome sequence of a novel avian paramyxovirus

Molecular and phylogenetic analysis of a novel turkey-origin picobirnavirus

Genetic characterization of a novel duck-origin picornavirus with six 2A proteins

Genetic characterization of a novel picornavirus in turkeys (Meleagris gallopavo) distinct from turkey galliviruses and megriviruses and distantly related to the members of the genus Avihepatovirus

Identification and complete genome analysis of kobuvirus in faecal samples of European roller (Coracias garrulus): for the first time in a bird

Genetic characterization of a novel picornavirus distantly related to the marine mammal-infecting aquamaviruses in a long-distance migrant bird species, European roller (Coracias garrulus)

Molecular detection of novel picornaviruses in chickens and turkeys

Identification and complete genome characterization of a novel picornavirus in turkey (Meleagris gallopavo)

Novel picornavirus in domesticated common quail (Coturnix coturnix) in Hungary

Identification and genetic characterization of a novel picornavirus from chickens

A novel mosquito-borne Orbivirus species found in South-east Asia

Outbreak-associated novel duck Reovirus, China

Characterization of Farmington virus, a novel virus from birds that is distantly related to members of the family Rhabdoviridae