Limits...
Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China.

Qiu S, Li P, Liu H, Wang Y, Liu N, Li C, Li S, Li M, Jiang Z, Sun H, Li Y, Xie J, Yang C, Wang J, Li H, Yi S, Wu Z, Jia L, Wang L, Hao R, Sun Y, Huang L, Ma H, Yuan Z, Song H - Sci Rep (2015)

Bottom Line: WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates.Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate.Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

View Article: PubMed Central - PubMed

Affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.

ABSTRACT
From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

No MeSH data available.


Related in: MedlinePlus

Phylogenetic analysis and pairwise alignment of the outbreak isolates based on DNA polymerase and VA RNA.Panels (A,C) represent the phylogenetic trees of DNA polymerase and VA RNA genes, respectively. Panels (B,D) represent the pairwise alignment analyses of the outbreak strains based on the DNA polymerase amino acid sequences and VA RNA genes, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4559894&req=5

f4: Phylogenetic analysis and pairwise alignment of the outbreak isolates based on DNA polymerase and VA RNA.Panels (A,C) represent the phylogenetic trees of DNA polymerase and VA RNA genes, respectively. Panels (B,D) represent the pairwise alignment analyses of the outbreak strains based on the DNA polymerase amino acid sequences and VA RNA genes, respectively.

Mentions: To rapidly measure the degree of genetic relatedness among the HAdV-7 isolates from the outbreak and non-recruit cases, WGS was performed on ten HAdV-7 isolates including those from the index cases. Genome sequences were deposited in the GenBank database (accession nos. KJ019879-KJ019888). By aligning the sequenced genomes and using 0901 HZ as a reference genome (accession no. JF800905), the nine outbreak isolates, including those from the index cases (accession nos. KJ019879, KJ019880 and KJ019885), were 100% identical. Phylogenetic analysis of the WGS showed that the outbreak isolates formed an independent sublineage among the HAdV-7 strains (Fig. 3A). Comparative genomic and phylogenetic analyses showed that the outbreak isolates had genomes nearly identical with an isolate CDC228 (accession no. KJ019884) identified from a local patient, as well as other five strains (accession nos. JF800905, KC440171, JX625134, KF268314 and KF268316) circulating in China61819. Further phylogenetic analysis of the individual whole genes revealed that the outbreak isolates clustered with the local isolate CDC228 as well as the above five strains, and shared 100% similarities in the hexon and fiber genes (Fig. 3B,C). However, the outbreak strains formed a separate subclade in the phylogenetic trees based on the penton, DNA polymerase and VA RNA genes (Figs 3D and 4A,C). Genome comparisons revealed that the outbreak isolates had only minor differences in the penton and DNA polymerase genes with CDC228 and the above reference strains (Table 3, Figs 3D and 4A), but a distinct point mutation was observed among them when compared with other HAdV-7 strains, resulting in the replacement of Leu381 with Ile (Table 3 and Fig. 4B). Additionally, all of the outbreak isolates showed an obvious difference with other HAdV-7 strains in the VA RNA genes (Fig. 4C), with a unique deletion of 12 base pair in the VA RNA II region (Table 3 and Fig. 4D). The universality of this unique deletion and the distinct point mutation were verified among an additional 46 HAdV-7 outbreak strains by PCR and DNA sequencing (data not shown).


Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China.

Qiu S, Li P, Liu H, Wang Y, Liu N, Li C, Li S, Li M, Jiang Z, Sun H, Li Y, Xie J, Yang C, Wang J, Li H, Yi S, Wu Z, Jia L, Wang L, Hao R, Sun Y, Huang L, Ma H, Yuan Z, Song H - Sci Rep (2015)

Phylogenetic analysis and pairwise alignment of the outbreak isolates based on DNA polymerase and VA RNA.Panels (A,C) represent the phylogenetic trees of DNA polymerase and VA RNA genes, respectively. Panels (B,D) represent the pairwise alignment analyses of the outbreak strains based on the DNA polymerase amino acid sequences and VA RNA genes, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559894&req=5

f4: Phylogenetic analysis and pairwise alignment of the outbreak isolates based on DNA polymerase and VA RNA.Panels (A,C) represent the phylogenetic trees of DNA polymerase and VA RNA genes, respectively. Panels (B,D) represent the pairwise alignment analyses of the outbreak strains based on the DNA polymerase amino acid sequences and VA RNA genes, respectively.
Mentions: To rapidly measure the degree of genetic relatedness among the HAdV-7 isolates from the outbreak and non-recruit cases, WGS was performed on ten HAdV-7 isolates including those from the index cases. Genome sequences were deposited in the GenBank database (accession nos. KJ019879-KJ019888). By aligning the sequenced genomes and using 0901 HZ as a reference genome (accession no. JF800905), the nine outbreak isolates, including those from the index cases (accession nos. KJ019879, KJ019880 and KJ019885), were 100% identical. Phylogenetic analysis of the WGS showed that the outbreak isolates formed an independent sublineage among the HAdV-7 strains (Fig. 3A). Comparative genomic and phylogenetic analyses showed that the outbreak isolates had genomes nearly identical with an isolate CDC228 (accession no. KJ019884) identified from a local patient, as well as other five strains (accession nos. JF800905, KC440171, JX625134, KF268314 and KF268316) circulating in China61819. Further phylogenetic analysis of the individual whole genes revealed that the outbreak isolates clustered with the local isolate CDC228 as well as the above five strains, and shared 100% similarities in the hexon and fiber genes (Fig. 3B,C). However, the outbreak strains formed a separate subclade in the phylogenetic trees based on the penton, DNA polymerase and VA RNA genes (Figs 3D and 4A,C). Genome comparisons revealed that the outbreak isolates had only minor differences in the penton and DNA polymerase genes with CDC228 and the above reference strains (Table 3, Figs 3D and 4A), but a distinct point mutation was observed among them when compared with other HAdV-7 strains, resulting in the replacement of Leu381 with Ile (Table 3 and Fig. 4B). Additionally, all of the outbreak isolates showed an obvious difference with other HAdV-7 strains in the VA RNA genes (Fig. 4C), with a unique deletion of 12 base pair in the VA RNA II region (Table 3 and Fig. 4D). The universality of this unique deletion and the distinct point mutation were verified among an additional 46 HAdV-7 outbreak strains by PCR and DNA sequencing (data not shown).

Bottom Line: WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates.Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate.Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

View Article: PubMed Central - PubMed

Affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.

ABSTRACT
From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

No MeSH data available.


Related in: MedlinePlus