Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection

ABSTRACT Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jeong Yoon Lee, Ji Sun Lee, Emma C. Materne, Rahul Rajala, Ashrafali M. Ismail, Donald Seto, David W. Dyer, Jaya Rajaiya, James Chodosh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	adenoviruses commensal homologous recombination Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ffe2324aec3f48e59fea24b7d3d2bd13
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ffe2324aec3f48e59fea24b7d3d2bd13
record_format	dspace
spelling	oai:doaj.org-article:ffe2324aec3f48e59fea24b7d3d2bd132021-11-15T15:24:22ZBacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection10.1128/mSphere.00105-182379-5042https://doaj.org/article/ffe2324aec3f48e59fea24b7d3d2bd132018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00105-18https://doaj.org/toc/2379-5042ABSTRACT Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as ChiAD, were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to ChiAD sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.Jeong Yoon LeeJi Sun LeeEmma C. MaterneRahul RajalaAshrafali M. IsmailDonald SetoDavid W. DyerJaya RajaiyaJames ChodoshAmerican Society for Microbiologyarticleadenovirusescommensalhomologous recombinationMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	adenoviruses commensal homologous recombination Microbiology QR1-502
spellingShingle	adenoviruses commensal homologous recombination Microbiology QR1-502 Jeong Yoon Lee Ji Sun Lee Emma C. Materne Rahul Rajala Ashrafali M. Ismail Donald Seto David W. Dyer Jaya Rajaiya James Chodosh Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
description	ABSTRACT Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as ChiAD, were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to ChiAD sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota.
format	article
author	Jeong Yoon Lee Ji Sun Lee Emma C. Materne Rahul Rajala Ashrafali M. Ismail Donald Seto David W. Dyer Jaya Rajaiya James Chodosh
author_facet	Jeong Yoon Lee Ji Sun Lee Emma C. Materne Rahul Rajala Ashrafali M. Ismail Donald Seto David W. Dyer Jaya Rajaiya James Chodosh
author_sort	Jeong Yoon Lee
title	Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
title_short	Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
title_full	Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
title_fullStr	Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
title_full_unstemmed	Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection
title_sort	bacterial reca protein promotes adenoviral recombination during <italic toggle="yes">in vitro</italic> infection
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ffe2324aec3f48e59fea24b7d3d2bd13
work_keys_str_mv	AT jeongyoonlee bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT jisunlee bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT emmacmaterne bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT rahulrajala bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT ashrafalimismail bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT donaldseto bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT davidwdyer bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT jayarajaiya bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection AT jameschodosh bacterialrecaproteinpromotesadenoviralrecombinationduringitalictoggleyesinvitroitalicinfection
_version_	1718427987706118144

Bacterial RecA Protein Promotes Adenoviral Recombination during <italic toggle="yes">In Vitro</italic> Infection

Ejemplares similares