REVIEW EDITORIAL For reprint orders, please contact: [email protected]
Do nonhuman primate or bat adenoviruses pose a risk for human health?
“The probability that the next ‘big one’ will be due to a zoonotic adenovirus is remote.”
Mária Benkő1, Balázs Harrach1 & Eric J Kremer*,2,3,4 Adenoviruses (AdVs) are nonenveloped dsDNA viruses with a genome ranging between 26 and 48 kilobase pairs and with approximately a dozen structural proteins [1] . The family Adenoviridae is presently divided into five genera, of which the genus Mastadenovirus contains isolates derived from mammals [2] . The other four genera largely correspond to lineages infecting different major groups (birds, scaled reptiles or fish) of vertebrates [3] . AdV virions have an icosahedral capsid of approximately 70−110 nm, with the external surface mainly being composed of hexon, penton base and fiber. Hexon is the major structural protein. The trimeric fiber is an elongated thread-like molecule that projects from the penton base, which is located at each of the 12 vertices. At least in vitro, the fiber knob domain of many AdVs engages cell surface molecules such as CAR, CD46, CD80, sialic acids and desmoglein 2 [4] . Some AdVs have two fiber genes coding for proteins of different length, receptor use and affinity,
which together likely enable a wider tissue tropism and/or host range. More than 50 human AdV (HAdV) types have been classified into species – HAdV-A to HAdV-G. HAdVs have been extensively studied because of their tendency to induce mild respiratory, ocular and enteric diseases in immunecompetent individuals. Although rare, in immune-deficient patients, AdVs can cause severe disease or even death [5] . In addition, AdVs have been engineered into potent gene-transfer vectors. Owing to recent coronavirus outbreaks (SARS-CoV in 2003 and MERS-CoV in 2010) and the recurring influenza scares (H5N1 since 1997 and H7N9 in 2013), the topic of zoonotic viruses, that is, viruses that jump from their natural host to eventually cause diseases in humans, has made headlines. Recently, we were asked if nonhuman primate or bat AdVs (BtAdVs) pose a risk for human health. As with any virus host switching, several basic requirements and key events need to occur.
KEYWORDS
• adenovirus • bat • chimpanzee • host switching • monkey • zoonosis
Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1581 Budapest, Hungary 2 Institut de Génétique Moléculaire de Montpellier, CNRS 5535, Montpellier, France 3 Université de Montpellier I, Montpellier, France 4 Université de Montpellier II, Montpellier, France *Author for correspondence: Tel.: +33 4 3435 9674; Fax: +33 3435 9634; [email protected] 1
10.2217/FMB.13.170 © 2014 Future Medicine Ltd
Future Microbiol. (2014) 9(3), 269–272
part of
ISSN 1746-0913
269
Editorial Benkő, Harrach & Kremer Contact with the reservoirs Although uncommon in Europe and North America, being in close proximity to nonhuman primates (different monkeys and chimpanzees) is not rare in Africa or Asia. However, the tendency for humans to kill and eat monkeys may provide opportunities for more efficient transmission of pathogens, as has been proposed for HIV host switching. In addition, nonhuman primate breeding colonies may also create inherent risks for humans. In the case of bats, they are also captured and used by humans for food and/or medicines. In addition to direct contact, human encroachment on bat dwellings, and the propensity for aerosol transmission from bat urine and guano, increases the probability to come in contact with BtAdVs. It is very likely that humans have been repeatedly infected with BtAdVs, but we are unaware of evidence that demonstrates that they have propagated in humans. Nonetheless, some BtAdVs can propagate in human cells [6] , and some HAdV can propagate in bat cells [Shi Z, Pers. Comm.] .
“...there are recent cases
when monkey adenoviruses infected the caretaker (direct exposure) and the infection might have spread further to family members.”
270
Receptors Unlike the scenario with influenza and corona viruses, the key determinant for AdV infection is unlikely to be primarily receptor usage. For example, CAR, a member of the superimmuno globulin family, is highly conserved between species and expressed by many tissues. Vectors derived from canine AdV (CAdV) type 2 (CAdV-2) and some HAdVs can use CAR to transduce rodent, cat, dog, bat, primate and even fish cells. CD46, first identified as a regulator of complement activation, is a receptor for a variety of pathogens, including some HAdV-B species. Importantly, nonhuman primates and bats also express CD46 by many tissues and cell types. Host switching AdVs possibly evolved from a bacterial virus that infected an ancestral host [7] , most likely near the ramification of the major vertebrate lineages. The organization of the central genome, encoding the structural proteins, is highly conserved, whereas the early regions at the genome ends encode regulatory proteins that interact with the host cells. Accordingly, the size and content of the AdV genome extremities show large variations among the different genera. Although moderate differences exist among AdVs within a given genus, AdVs usually infect one or closely related species; however, there are AdVs with a rather
Future Microbiol. (2014) 9(3)
broad host range: CAdV-1 and -2, with or without clinical disease, has been detected in other carnivorous animals including coyotes, bears, jackals, pandas, skunks and wolves [8] . The two types of CAdV (1 and 2) are so serologically similar that an attenuated strain of CAdV-2, which causes mild upper respiratory track disease in dogs, can be used as a safe and efficient vaccine against CAdV-1, which causes a severe infectious canine hepatitis. Recent phylogenetic analyses of BtAdVs showed that the clade of the vespertilionid BtAdVs flank CAdV-1/2 [9,10] . This clustering was further strengthened by the striking similarity in the content of E3 and E4 of CAdV-1/2 and BtAdV-2 and 3, respectively [10] . It is possible that a BtAdV jumped to a Canidae family member, and later spread to related species. However, in spite of the long and close contact, transmission of CAdVs (via the domestication of dogs) to humans has not been documented. Furthermore, in spite of several efforts, we have been unable to propagate CAdV-2 in human cells [Kremer EJ, Unpublished Data] . From other phylogenetic analyses, it is clear that at least one chimpanzee AdV (ChAdV) found humans to be a receptive host. HAdV type 4 (HAdV-4) was among the first ‘human’ isolates, in part due to its prevalence, ability to propagate in culture monkey cells and ability to cause severe disease in North American military recruits. Although numerous ChAdVs are members of this species, EHAdV-4 is the only ‘human’ member species. In addition, HAdV-4 has never been found outside humans, which suggests significant adaptation and/or recombination. Other simian AdVs transmitted to humans were proposed [11,12] , and there are recent cases when monkey AdVs infected the caretaker (direct exposure) and the infection might have spread further to family members [13–15] . However, human-to-human spreading could not be unequivocally demonstrated as it was recognized and studied retrospectively. Mutations that facilitate host switching One fundamental difference in the recent corona virus and influenza virus jumps is that they are RNA viruses, and possess notoriously error-prone polymerases. Although the AdV polymerase has a significantly higher fidelity, the infected cell produces up to 10,000 viral genomes. While AdV polymerase-induced errors may play a role, the most likely scenario for adaptation to a new host is via recombination with a latent ‘host-specific’
future science group
Do nonhuman primate or bat adenoviruses pose a risk for human health? AdV. This appears to be the primary source of ‘novel’ HAdVs that have been identified in the last 10 years. However, approximately 25 years ago it was suggested that some HAdVs poorly propagate in monkeys cells due to the lack of efficient interactions with the host proteins, but this could be circumvented when SV40 sequences are incorporated into the AdV genome. More specifically, the products of the HAdV E1, E3 and/or E4 regions must interact with cellular proteins to circumvent the host innate response and initiate the cell cycle. Significant variation between the interactions of AdVs and host cell proteins would preclude efficient propagation in some, but clearly not all, species. Spread One commonly disseminated belief concerning virus spreading is that if a host becomes too sick, or dies too quickly, the virus would die off due to the lack of another vector. In healthy hosts, persistent HAdV, CAdV, BtAdV and ChAdV infections appear to be common (for example see [16]). Epidemiology studies reported that the majority of us have been exposed to multiple HAdV types by the time we were 10 years old, and we harbor a crossreacting humoral and cellular response against many HAdVs. Owing to the ubiquitous nature of HAdV infections in humans, and the widespread humoral and cellular responses in almost all populations, the risk for a pandemic non-HAdV infection causing severe pandemic disease in adults would appear restricted. While the presence of anti-AdV antibodies would seem critical to prevent infections and propagation, it is the T-cell response (CD4 +/CD8 + cytotoxic T lymphocytes) that rapidly destroys infected cells and protects us from AdV disease. Notably, patients that are B-cell deficient control AdV infections, while the lack of a T-cell response can allow AdVs to be lethal. Fortunately, the antiHAdV T-cell response is also ubiquitous in adult humans, and is partly directed against conserved epitopes buried in the internal region of hexon.
Horwitz M. Adenoviruses. In: Fields Virology. Fields B, Knipe D (Eds). Raven Press, PA, USA, 2149–2171 (2001).
2
Available adenovirus sequences. www.vmri.hu/∼harrach/ADENOSEQ.HTM
3
Harrach B, Benkő M, Both G. Family Adenoviridae. In: Virus Taxonomy. King A,
future science group
“Adenovirsues have and will continue to switch hosts; however, the likelihood for serious pandemic infections is tempered by several factors.”
Financial & competing interests disclosure This work was supported by grants from the European Commission through the 7th Framework Programs: ADVance (#290002) to M Benk, B Harrach and EJ Kremer; and BrainCAV (#222992) to EJ Kremer. This work was also supported by the Region Languedoc Roussillon, the Fondation de France, Vaincre les Maladies Lysosomales, Agence National de la Recherche and the Association Française contre les Myopathies to EJ Kremer; and grant OTKA NN107632 provided by Hungarian Scientific Research Fund to B Harrach and M Benk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was used in the production of this manuscript.
Adams M, Carstens E, Lefkowitz EJ (Eds). Elsevier, Oxford, UK, 125–141 (2011).
References 1
Likely due to structural constraints, this region of the AdV capsid is well conserved and would be a ready target for the T-cell response in most healthy individuals infected with a zoonotic AdV. Will nonhuman primate AdVs or BtAdVs pose a risk for human health? AdVs have and will continue to switch hosts; however, the likelihood for serious pandemic infections is tempered by several factors. Although, the lessons from morbidity and mortality caused by HAdV-4 in young, healthy military recruits put under extreme physical and emotional stress in dense populations need to be heeded. The probability that the next ‘big one’ will be due to a zoonotic AdV is remote. However, there are groups that will have greater risks than others, in particular children that have not been exposed to numerous selflimiting HAdV infections, the aged population whose pathogen surveillance has diminished, immunosuppressed individuals and others in challenging situations like the military recruits. So, as Voltaire responded on his deathbed to a priest asking him that he renounce Satan: “Now, now my good man, this is no time to be making enemies”.
Editorial
patients. Br. J. Haematol. 128(2), 135–144 (2005).
4
Arnberg N. Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol. Sci. 33(8), 442–448 (2012).
6
Li Y, Ge X, Zhang H et al. Host range, prevalence, and genetic diversity of adenoviruses in bats. J. Virol. 84(8), 3889–3897 (2010).
5
Leen AM, Rooney CM. Adenovirus as an emerging pathogen in immunocompromised
7
Benson SD, Bamford JK, Bamford DH, Burnett RM. Does common architecture
www.futuremedicine.com
271
Editorial Benkő, Harrach & Kremer reveal a viral lineage spanning all three domains of life? Mol. Cell 16(5), 673–685 (2004). 8
9
Philippa JD, Leighton FA, Daoust PY et al. Antibodies to selected pathogens in free-ranging terrestrial carnivores and marine mammals in Canada. Vet. Rec. 155(5), 135–140 (2004). Janoska M, Vidovszky M, Molnar V, Liptovszky M, Harrach B, Benko M. Novel adenoviruses and herpesviruses detected in bats. Vet. J. 189(1), 118–121 (2010).
10 Kohl C, Vidovszky MZ, Muhldorfer K et al.
Genome analysis of bat adenovirus 2:
272
indications of interspecies transmission. J. Virol. 86(3), 1888–1892 (2012). 11 Xiang Z, Li Y, Cun A et al. Chimpanzee
adenovirus antibodies in humans, SubSaharan Africa. Emerg. Infect. Dis. 12(10), 1596–1599 (2006). 12 Wevers D, Metzger S, Babweteera F et al.
Novel adenoviruses in wild primates: a high level of genetic diversity and evidence of zoonotic transmissions. J. Virol. 85(20), 10774–10784 (2011). 13 Chen EC, Yagi S, Kelly KR et al. Cross-
species transmission of a novel adenovirus associated with a fulminant pneumonia outbreak in a new world monkey colony. PLoS Pathog. 7(7), e1002155 (2011).
Future Microbiol. (2014) 9(3)
14 Chiu CY, Yagi S, Lu X et al. A novel
adenovirus species associated with an acute respiratory outbreak in a baboon colony and evidence of coincident human infection. mBio 4(2), e00084 (2013). 15 Yu G, Yagi S, Carrion R Jr et al. Experimental
cross-species infection of common marmosets by titi monkey adenovirus. PLoS ONE 8(7), e68558 (2013). 16 Roy S, Vandenberghe LH, Kryazhimskiy S
et al. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates. PLoS Pathog. 5(7), e1000503 (2009).
future science group
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
Do nonhuman primate or bat adenoviruses pose a risk for human health?
“The probability that the next ‘big one’ will be due to a zoonotic adenovirus is remote.”
Mária Benkő1, Balázs Harrach1 & Eric J Kremer*,2,3,4 Adenoviruses (AdVs) are nonenveloped dsDNA viruses with a genome ranging between 26 and 48 kilobase pairs and with approximately a dozen structural proteins [1] . The family Adenoviridae is presently divided into five genera, of which the genus Mastadenovirus contains isolates derived from mammals [2] . The other four genera largely correspond to lineages infecting different major groups (birds, scaled reptiles or fish) of vertebrates [3] . AdV virions have an icosahedral capsid of approximately 70−110 nm, with the external surface mainly being composed of hexon, penton base and fiber. Hexon is the major structural protein. The trimeric fiber is an elongated thread-like molecule that projects from the penton base, which is located at each of the 12 vertices. At least in vitro, the fiber knob domain of many AdVs engages cell surface molecules such as CAR, CD46, CD80, sialic acids and desmoglein 2 [4] . Some AdVs have two fiber genes coding for proteins of different length, receptor use and affinity,
which together likely enable a wider tissue tropism and/or host range. More than 50 human AdV (HAdV) types have been classified into species – HAdV-A to HAdV-G. HAdVs have been extensively studied because of their tendency to induce mild respiratory, ocular and enteric diseases in immunecompetent individuals. Although rare, in immune-deficient patients, AdVs can cause severe disease or even death [5] . In addition, AdVs have been engineered into potent gene-transfer vectors. Owing to recent coronavirus outbreaks (SARS-CoV in 2003 and MERS-CoV in 2010) and the recurring influenza scares (H5N1 since 1997 and H7N9 in 2013), the topic of zoonotic viruses, that is, viruses that jump from their natural host to eventually cause diseases in humans, has made headlines. Recently, we were asked if nonhuman primate or bat AdVs (BtAdVs) pose a risk for human health. As with any virus host switching, several basic requirements and key events need to occur.
KEYWORDS
• adenovirus • bat • chimpanzee • host switching • monkey • zoonosis
Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1581 Budapest, Hungary 2 Institut de Génétique Moléculaire de Montpellier, CNRS 5535, Montpellier, France 3 Université de Montpellier I, Montpellier, France 4 Université de Montpellier II, Montpellier, France *Author for correspondence: Tel.: +33 4 3435 9674; Fax: +33 3435 9634; [email protected] 1
10.2217/FMB.13.170 © 2014 Future Medicine Ltd
Future Microbiol. (2014) 9(3), 269–272
part of
ISSN 1746-0913
269
Editorial Benkő, Harrach & Kremer Contact with the reservoirs Although uncommon in Europe and North America, being in close proximity to nonhuman primates (different monkeys and chimpanzees) is not rare in Africa or Asia. However, the tendency for humans to kill and eat monkeys may provide opportunities for more efficient transmission of pathogens, as has been proposed for HIV host switching. In addition, nonhuman primate breeding colonies may also create inherent risks for humans. In the case of bats, they are also captured and used by humans for food and/or medicines. In addition to direct contact, human encroachment on bat dwellings, and the propensity for aerosol transmission from bat urine and guano, increases the probability to come in contact with BtAdVs. It is very likely that humans have been repeatedly infected with BtAdVs, but we are unaware of evidence that demonstrates that they have propagated in humans. Nonetheless, some BtAdVs can propagate in human cells [6] , and some HAdV can propagate in bat cells [Shi Z, Pers. Comm.] .
“...there are recent cases
when monkey adenoviruses infected the caretaker (direct exposure) and the infection might have spread further to family members.”
270
Receptors Unlike the scenario with influenza and corona viruses, the key determinant for AdV infection is unlikely to be primarily receptor usage. For example, CAR, a member of the superimmuno globulin family, is highly conserved between species and expressed by many tissues. Vectors derived from canine AdV (CAdV) type 2 (CAdV-2) and some HAdVs can use CAR to transduce rodent, cat, dog, bat, primate and even fish cells. CD46, first identified as a regulator of complement activation, is a receptor for a variety of pathogens, including some HAdV-B species. Importantly, nonhuman primates and bats also express CD46 by many tissues and cell types. Host switching AdVs possibly evolved from a bacterial virus that infected an ancestral host [7] , most likely near the ramification of the major vertebrate lineages. The organization of the central genome, encoding the structural proteins, is highly conserved, whereas the early regions at the genome ends encode regulatory proteins that interact with the host cells. Accordingly, the size and content of the AdV genome extremities show large variations among the different genera. Although moderate differences exist among AdVs within a given genus, AdVs usually infect one or closely related species; however, there are AdVs with a rather
Future Microbiol. (2014) 9(3)
broad host range: CAdV-1 and -2, with or without clinical disease, has been detected in other carnivorous animals including coyotes, bears, jackals, pandas, skunks and wolves [8] . The two types of CAdV (1 and 2) are so serologically similar that an attenuated strain of CAdV-2, which causes mild upper respiratory track disease in dogs, can be used as a safe and efficient vaccine against CAdV-1, which causes a severe infectious canine hepatitis. Recent phylogenetic analyses of BtAdVs showed that the clade of the vespertilionid BtAdVs flank CAdV-1/2 [9,10] . This clustering was further strengthened by the striking similarity in the content of E3 and E4 of CAdV-1/2 and BtAdV-2 and 3, respectively [10] . It is possible that a BtAdV jumped to a Canidae family member, and later spread to related species. However, in spite of the long and close contact, transmission of CAdVs (via the domestication of dogs) to humans has not been documented. Furthermore, in spite of several efforts, we have been unable to propagate CAdV-2 in human cells [Kremer EJ, Unpublished Data] . From other phylogenetic analyses, it is clear that at least one chimpanzee AdV (ChAdV) found humans to be a receptive host. HAdV type 4 (HAdV-4) was among the first ‘human’ isolates, in part due to its prevalence, ability to propagate in culture monkey cells and ability to cause severe disease in North American military recruits. Although numerous ChAdVs are members of this species, EHAdV-4 is the only ‘human’ member species. In addition, HAdV-4 has never been found outside humans, which suggests significant adaptation and/or recombination. Other simian AdVs transmitted to humans were proposed [11,12] , and there are recent cases when monkey AdVs infected the caretaker (direct exposure) and the infection might have spread further to family members [13–15] . However, human-to-human spreading could not be unequivocally demonstrated as it was recognized and studied retrospectively. Mutations that facilitate host switching One fundamental difference in the recent corona virus and influenza virus jumps is that they are RNA viruses, and possess notoriously error-prone polymerases. Although the AdV polymerase has a significantly higher fidelity, the infected cell produces up to 10,000 viral genomes. While AdV polymerase-induced errors may play a role, the most likely scenario for adaptation to a new host is via recombination with a latent ‘host-specific’
future science group
Do nonhuman primate or bat adenoviruses pose a risk for human health? AdV. This appears to be the primary source of ‘novel’ HAdVs that have been identified in the last 10 years. However, approximately 25 years ago it was suggested that some HAdVs poorly propagate in monkeys cells due to the lack of efficient interactions with the host proteins, but this could be circumvented when SV40 sequences are incorporated into the AdV genome. More specifically, the products of the HAdV E1, E3 and/or E4 regions must interact with cellular proteins to circumvent the host innate response and initiate the cell cycle. Significant variation between the interactions of AdVs and host cell proteins would preclude efficient propagation in some, but clearly not all, species. Spread One commonly disseminated belief concerning virus spreading is that if a host becomes too sick, or dies too quickly, the virus would die off due to the lack of another vector. In healthy hosts, persistent HAdV, CAdV, BtAdV and ChAdV infections appear to be common (for example see [16]). Epidemiology studies reported that the majority of us have been exposed to multiple HAdV types by the time we were 10 years old, and we harbor a crossreacting humoral and cellular response against many HAdVs. Owing to the ubiquitous nature of HAdV infections in humans, and the widespread humoral and cellular responses in almost all populations, the risk for a pandemic non-HAdV infection causing severe pandemic disease in adults would appear restricted. While the presence of anti-AdV antibodies would seem critical to prevent infections and propagation, it is the T-cell response (CD4 +/CD8 + cytotoxic T lymphocytes) that rapidly destroys infected cells and protects us from AdV disease. Notably, patients that are B-cell deficient control AdV infections, while the lack of a T-cell response can allow AdVs to be lethal. Fortunately, the antiHAdV T-cell response is also ubiquitous in adult humans, and is partly directed against conserved epitopes buried in the internal region of hexon.
Horwitz M. Adenoviruses. In: Fields Virology. Fields B, Knipe D (Eds). Raven Press, PA, USA, 2149–2171 (2001).
2
Available adenovirus sequences. www.vmri.hu/∼harrach/ADENOSEQ.HTM
3
Harrach B, Benkő M, Both G. Family Adenoviridae. In: Virus Taxonomy. King A,
future science group
“Adenovirsues have and will continue to switch hosts; however, the likelihood for serious pandemic infections is tempered by several factors.”
Financial & competing interests disclosure This work was supported by grants from the European Commission through the 7th Framework Programs: ADVance (#290002) to M Benk, B Harrach and EJ Kremer; and BrainCAV (#222992) to EJ Kremer. This work was also supported by the Region Languedoc Roussillon, the Fondation de France, Vaincre les Maladies Lysosomales, Agence National de la Recherche and the Association Française contre les Myopathies to EJ Kremer; and grant OTKA NN107632 provided by Hungarian Scientific Research Fund to B Harrach and M Benk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was used in the production of this manuscript.
Adams M, Carstens E, Lefkowitz EJ (Eds). Elsevier, Oxford, UK, 125–141 (2011).
References 1
Likely due to structural constraints, this region of the AdV capsid is well conserved and would be a ready target for the T-cell response in most healthy individuals infected with a zoonotic AdV. Will nonhuman primate AdVs or BtAdVs pose a risk for human health? AdVs have and will continue to switch hosts; however, the likelihood for serious pandemic infections is tempered by several factors. Although, the lessons from morbidity and mortality caused by HAdV-4 in young, healthy military recruits put under extreme physical and emotional stress in dense populations need to be heeded. The probability that the next ‘big one’ will be due to a zoonotic AdV is remote. However, there are groups that will have greater risks than others, in particular children that have not been exposed to numerous selflimiting HAdV infections, the aged population whose pathogen surveillance has diminished, immunosuppressed individuals and others in challenging situations like the military recruits. So, as Voltaire responded on his deathbed to a priest asking him that he renounce Satan: “Now, now my good man, this is no time to be making enemies”.
Editorial
patients. Br. J. Haematol. 128(2), 135–144 (2005).
4
Arnberg N. Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol. Sci. 33(8), 442–448 (2012).
6
Li Y, Ge X, Zhang H et al. Host range, prevalence, and genetic diversity of adenoviruses in bats. J. Virol. 84(8), 3889–3897 (2010).
5
Leen AM, Rooney CM. Adenovirus as an emerging pathogen in immunocompromised
7
Benson SD, Bamford JK, Bamford DH, Burnett RM. Does common architecture
www.futuremedicine.com
271
Editorial Benkő, Harrach & Kremer reveal a viral lineage spanning all three domains of life? Mol. Cell 16(5), 673–685 (2004). 8
9
Philippa JD, Leighton FA, Daoust PY et al. Antibodies to selected pathogens in free-ranging terrestrial carnivores and marine mammals in Canada. Vet. Rec. 155(5), 135–140 (2004). Janoska M, Vidovszky M, Molnar V, Liptovszky M, Harrach B, Benko M. Novel adenoviruses and herpesviruses detected in bats. Vet. J. 189(1), 118–121 (2010).
10 Kohl C, Vidovszky MZ, Muhldorfer K et al.
Genome analysis of bat adenovirus 2:
272
indications of interspecies transmission. J. Virol. 86(3), 1888–1892 (2012). 11 Xiang Z, Li Y, Cun A et al. Chimpanzee
adenovirus antibodies in humans, SubSaharan Africa. Emerg. Infect. Dis. 12(10), 1596–1599 (2006). 12 Wevers D, Metzger S, Babweteera F et al.
Novel adenoviruses in wild primates: a high level of genetic diversity and evidence of zoonotic transmissions. J. Virol. 85(20), 10774–10784 (2011). 13 Chen EC, Yagi S, Kelly KR et al. Cross-
species transmission of a novel adenovirus associated with a fulminant pneumonia outbreak in a new world monkey colony. PLoS Pathog. 7(7), e1002155 (2011).
Future Microbiol. (2014) 9(3)
14 Chiu CY, Yagi S, Lu X et al. A novel
adenovirus species associated with an acute respiratory outbreak in a baboon colony and evidence of coincident human infection. mBio 4(2), e00084 (2013). 15 Yu G, Yagi S, Carrion R Jr et al. Experimental
cross-species infection of common marmosets by titi monkey adenovirus. PLoS ONE 8(7), e68558 (2013). 16 Roy S, Vandenberghe LH, Kryazhimskiy S
et al. Isolation and characterization of adenoviruses persistently shed from the gastrointestinal tract of non-human primates. PLoS Pathog. 5(7), e1000503 (2009).
future science group
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.
