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Deep analysis of Loop L1 HVRs1-4 region of the hexon gene of adenovirus field strains isolated in Poland.

ABSTRACT: BACKGROUND:To date, studies on loop L1 HVRs1-4 region of the hexon gene in fowl adenovirus genome (FAdVs) lack comprehensive molecular data. In this study detailed prospectively obtained sequences from field adenovirus strains, NVRI, Poland have been analyzed. METHODS:Overall hundred and thirty seven adenovirus strains were collected, evaluated, and examined of hyper variable loop L1 region HVRs1-4 of the hexon gene for the presence of similarity, mutations, tertiary structure, and spinal conformation. RESULTS:Sequences were characterized, and divided for five species and seven types, FAdV-A-E/FAdV-1/2/4/5/7/8a/8b/11. The presence of predicted tertiary structure depending on type/species were determined. Analysis of specific selected sequences: GQMTN 1/A, 7/E, and 8b/E, GQMTT 2/11/D, GQLSN 4/C, GQMTH 5/B, and GQMSN 8a/E in examined HVRs1-4 Loop L1 region of hexon gene compared to tertiary structure indicated that this visibly conservative region represents the antigenic binging activity. CONCLUSION:This is the first molecular study on tertiary structure on HVRs1-4 region in adenovirus genome conducted in Poland. Analysis indicated specific sequence in Loop L1 HVR1-4 region which is strictly responsible for antibodies binding. This information could assist during the process connected with specific preventive strategies based on their molecular genome investigation and new facilitate studies. This study will help to better understand the mechanisms of pathogenicity of adenovirus strains provide a guide for disease control in birds.

SUBMITTER: Niczyporuk JS

PROVIDER: S-EPMC6258537 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Deep analysis of Loop L1 HVRs1-4 region of the hexon gene of adenovirus field strains isolated in Poland.

Niczyporuk Jowita Samanta JS

PloS one 20181127 11

<h4>Background</h4>To date, studies on loop L1 HVRs1-4 region of the hexon gene in fowl adenovirus genome (FAdVs) lack comprehensive molecular data. In this study detailed prospectively obtained sequences from field adenovirus strains, NVRI, Poland have been analyzed.<h4>Methods</h4>Overall hundred and thirty seven adenovirus strains were collected, evaluated, and examined of hyper variable loop L1 region HVRs1-4 of the hexon gene for the presence of similarity, mutations, tertiary structure, an ...[more]

PMID: 30481218

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Project description:Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype 4 (FAdV-4) has caused huge economic losses to poultry industries. The key genes responsible for different virulence of FAdV-4 strains are not fully elucidated. Previous studies indicated that hexon of pathogenic FAdV-4 has a conserved arginine (R) at position 188, and a conserved isoleucine (I) is present at this position in reported nonpathogenic FAdV-4. Recently, it was reported that R188 of hexon is the determinant site for pathogenicity of the emerging Chinese FAdV-4 strain. However, the role of hexon amino acid 188 (aa188) has not been examined in the nonpathogenic FAdV-4 strain. In this study, three recombinant FAdV-4 viruses, H/H/R188I, O/O/I188R, and H/O/I188R, were constructed by mutating hexon aa188 of FAdV-4 pathogenic strain CH/HNJZ/2015 (H) and nonpathogenic strain ON1 (O), and pathogenicity was assessed in specific-pathogen-free (SPF) chickens. Consistent with previous findings, H/O/I188R exhibited pathogenicity similar to that of CH/HNJZ/2015, yet H/H/R188I induced no mortality. Unexpectedly, all chickens infected with O/O/I188R survived. Postmortem examination of O/O/I188R-infected chickens showed typical lesions of inclusion body hepatitis rather than HHS. Expression of proinflammatory cytokines in CH/HNJZ/2015- and H/O/I188R-infected chickens was significantly higher than that in H/H/R188I-, ON1-, and O/O/I188R-infected chickens. Analysis of predicted hexon protein structures indicated that aa188 mutation leads to conformational changes in the L1 loop of HNJZ-hexon but not in ON1-hexon. In summary, the present study demonstrated that the role of hexon aa188 in the virulence of FAdV-4 varies between different strains. Induction of HHS requires factors aside from hexon aa188 in the emerging Chinese FAdV-4 strain. IMPORTANCE HHS induced by FAdV-4 has caused huge economic losses to the poultry industry. The key determinants for the different virulence of FAdV-4 have not been fully elucidated. Here, we investigated the role of hexon aa188 in FAdV-4 strains with different virulence and showed that the role of hexon aa188 varies in FAdV-4 strains with different genetic contents. The hexon R188 may be the key amino acid for causing inclusion body hepatitis by the pathogenic FAdV-4 strain, and induction of HHS by FAdV-4 may need other viral cofactors. Moreover, the hexon R188I mutation greatly affected the expression of proinflammatory cytokines induced by the pathogenic strain CH/HNJZ/2015, but no significant difference was observed between the nonpathogenic strain ON1 and ON1 with hexon I188R mutation. We found that hexon aa188 mutation induced conformational changes to hexon protein in CH/HNJZ/2015 but not in ON1, which might be the underlying reason for the changing virulence.

Project description:The aim of this study was to characterise the nucleotide and amino acid sequence of complete genomes (7.5 kb) from RHDV strains isolated in Poland and estimate the genetic variability in different elements of the viral RNA. In addition, the sequence of Polish RHDV isolates isolated from 1988-2015 was compared with the sequences of other European RHDV, including the RHDVa and RHDV2/RHDVb subtypes. The complete sequence was developed by the compilation of partial nucleotide sequences. This sequence consisted of approximately 7428 nucleotides. For comparison of nucleotide sequences and the development of phylogenetic trees of Polish RHDV isolates and reference RHDV strains representing the main phylogenetic groups of classical RHDV, RHDVa and RHDV2 as well as the non-pathogenic rabbit lagovirus RCV, the BLAST software with blastn and MEGA6 with neighbour-joining method was applied. The complete nucleotide sequence of Polish isolates of RHDV has also been entered into GenBank. For comparative analysis, nineteen complete sequences representing the main RHDV genetic types available in GenBank were used. The results of phylogenetic analysis of Polish RHDV strains reveals the presence of three classical RHDV genogroups (G2, G4 and G5) and an RHDVa variant (G6). The oldest RHDV isolates (KGM 1988, PD 1989 and MAL 1994) belong to genogroup G2. It can be assumed that the elimination of these strains from the environment probably occurred at the turn of 1994 and 1995. Genogroup G2 was replaced by the phylogenetically younger BLA 1994 and OPO 2004 strains from genogroup G4, which probably originated from the G3 lineage, represented by the Italian strains BS89. The last representatives of classical RHDV in Poland are isolates GSK 1988 and ZD0 2000 from genogroup G5. A single clade contains the Polish RHDV strains from 2004-2015 (GRZ 2004, KRY 2004, L145 2004, W147 2005, SKO 2013, GLE 2013, RED1 2013, STR 2012, STR2 2013, STR 2014, BIE 2015) identified as RHDVa, which clustered into genogroup G6, as represented by the RHDV strain Triptis 1996. All recent isolated RHDV isolates belong exclusively to RHDVa and no RHDV2 was diagnosed in Poland.

Dataset Information

Deep analysis of Loop L1 HVRs1-4 region of the hexon gene of adenovirus field strains isolated in Poland.

Publications

Deep analysis of Loop L1 HVRs1-4 region of the hexon gene of adenovirus field strains isolated in Poland.

Similar Datasets

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