Abstract

Human adenovirus type 55 (HAdV-B55) is a recently identified acute respiratory disease (ARD) pathogen in HAdV species B with a recombinant genome between renal HAdV-B11 and respiratory HAdV-B14. Since HAdV-B55 first appeared in China school in 2006, no more ARD cases associated with it had been reported until 2011, when there was an outbreak of adult severe community-acquired pneumonia (CAP) in Beijing, China. Reported here is the bioinformatics analysis of the re-emergent HAdV-B55 responsible for this outbreak. Recombination and protein sequence analysis re-confirmed that this isolate (BJ01) was a recombinant virus with the capsid hexon gene from HAdV-B11. The selection pressures for the three capsid proteins, i.e., hexon, penton base, and fiber genes, were all negative, along with very low non-synonymous (dN) and synonymous (dS) substitutions/site (<0.0007). Phylogenetic analyses of the whole genome and the three major capsid genes of HAdV-B55 revealed the close phylogenetic relationship among all HAdV-B55 strains. Comparative genomic analysis of this re-emergent HAdV-B55 strain (BJ01; 2011) with the first HAdV-B55 strain (QS-DLL; 2006) showed the high genome identity (99.87%), including 10 single-nucleotide non-synonymous substitutions, 11 synonymous substitutions, 3 insertions, and one deletion in non-coding regions. The major non-synonymous substitutions (6 of 10) occurred in the protein pVI in its L3 region, which protein has different functions at various stages of an adenovirus infection, and may be associated with the population distribution of HAdV-B55 infection. No non-synonymous substitutions were found in the three major capsid proteins, which proteins are responsible for type-specific neutralizing antibodies. Comparative genomic analysis of the re-emergent HAdV-B55 strains associated with adult severe CAP revealed conserved genome and capsid proteins, providing the foundation for the development of effective vaccines against this pathogen. This study also facilitates the further investigation of HAdV-B55 epidemiology, molecular evolution, patterns of pathogen emergence and re-emergence, and the predication of genome recombination between adenoviruses.

Highlights

  • Human adenoviruses (HAdV) are associated in humans with a broad spectrum of clinical diseases, such as acute respiratory disease (ARD), community-acquired pneumonia (CAP), as well as conjunctivitis, gastrointestinal, opportunistic infections in immune-deficient individuals, and possibly, obesity (Dingle and Langmuir, 1968; Chu and Pavan-Langston, 1979; Wood, 1988; Dhurandhar et al, 1992; Kojaoghlanian et al, 2003; Hakim and Tleyjeh, 2008)

  • Human adenoviruses are usually typed according to serum neutralization and hemagglutination-inhibition tests, both of which are associated with the three major capsid proteins, i.e., hexon, fiber, and penton base

  • 1http://hadvwg.gmu.edu students in a senior high school and one died during this outbreak (Zhu et al, 2009). Since this first isolate QS-DLL of HAdV-B55 was identified in 2006 (Yang et al, 2009; Walsh et al, 2010), no more ARD cases associated with this virus had been reported in China until 2011, when 16 HAdV-B55-like strains were identified based on partial gene sequencing in a CAP outbreak in Beijing, China in February and March (Cao et al, 2014)

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Summary

INTRODUCTION

Human adenoviruses (HAdV) are associated in humans with a broad spectrum of clinical diseases, such as acute respiratory disease (ARD), community-acquired pneumonia (CAP), as well as conjunctivitis, gastrointestinal, opportunistic infections in immune-deficient individuals, and possibly, obesity (Dingle and Langmuir, 1968; Chu and Pavan-Langston, 1979; Wood, 1988; Dhurandhar et al, 1992; Kojaoghlanian et al, 2003; Hakim and Tleyjeh, 2008). The strain QS-DLL is the first completely characterized HAdV-B55 based on the whole genomic analysis (Walsh et al, 2010) It caused an ARD outbreak in China, from March to April 2006, with 254 patients affected, of which 247 were. 1http://hadvwg.gmu.edu students in a senior high school and one died during this outbreak (Zhu et al, 2009) Since this first isolate QS-DLL of HAdV-B55 was identified in 2006 (Yang et al, 2009; Walsh et al, 2010), no more ARD cases associated with this virus had been reported in China until 2011, when 16 HAdV-B55-like strains were identified based on partial gene sequencing in a CAP outbreak in Beijing, China in February and March (Cao et al, 2014). The findings will contribute to the studies of the evolution and epidemiology of HAdV-B55, as well as provide both the foundation for the development of effective vaccines and public health strategies against this pathogen

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