Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus
Distinct clinical features of HBV infection have been associated with different viral genotype/subgenotype. HBV Genotype-D comprised of 10 subgenotypes, D1–D10, whose clinical implications still remain elusive. We investigated for the first-time, the virologic characteristics and cytopathic effects...
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| creator | Khatun, Mousumi Mondal, Rajiv Kumar Pal, Sourina Baidya, Ayana Bishnu, Debasree Banerjee, Priyanka Santra, Amal Kumar Dhali, Gopal Krishna Banerjee, Soma Chowdhury, Abhijit Datta, Simanti |
| description | Distinct clinical features of HBV infection have been associated with different viral genotype/subgenotype. HBV Genotype-D comprised of 10 subgenotypes, D1–D10, whose clinical implications still remain elusive. We investigated for the first-time, the virologic characteristics and cytopathic effects of four non-recombinant D-subgenotypes, D1/D2/D3/D5. Expressions of viral/host genes were evaluated in Huh7 cells transfected with full-length, linear-monomers of HBV/D-subgenotypes or pGL3-Basic vector carrying subgenotype-specific HBx. Intracellular HBV-DNA and pregenomic-RNA levels were high in D1/D2 than D3/D5. Expressions of PreC-mRNA and HBx were highest for D2 and D1 respectively, whereas PreS2/S-transcript was significantly reduced in D5. Increased apoptotic cell death and marked upregulation in caspase-3/Bax/TNF-R1/FasR/TRAIL-R1/ROS/MCP-1/IP-10/MIP-1β expression were noticed specifically in D2- and also in D3-transfected cells, while D5 resulted in over-expression of ER-stress-markers. D-subgenotype-transfected Huh7 cells were co-cultured with PBMC of healthy-donors or LX-2 cells and significant increase in pro-inflammatory cytokines in PBMC and fibrogenic-markers in LX-2 were noticed in presence of D2/D3. Further, Huh7 cells transfected with D1, in particular and also D5, displayed remarkable induction of EMT-markers and high proliferative/migratory abilities. Collectively, our results demonstrated that D2/D3 were more associated with hepatic apoptosis/inflammation/fibrosis and D1/D5 with increased risk of hepatocarcinogenesis and emphasize the need for determining HBV-subgenotype in clinical practice. |
| doi_str_mv | 10.1038/s41598-018-26414-4 |
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HBV Genotype-D comprised of 10 subgenotypes, D1–D10, whose clinical implications still remain elusive. We investigated for the first-time, the virologic characteristics and cytopathic effects of four non-recombinant D-subgenotypes, D1/D2/D3/D5. Expressions of viral/host genes were evaluated in Huh7 cells transfected with full-length, linear-monomers of HBV/D-subgenotypes or pGL3-Basic vector carrying subgenotype-specific HBx. Intracellular HBV-DNA and pregenomic-RNA levels were high in D1/D2 than D3/D5. Expressions of PreC-mRNA and HBx were highest for D2 and D1 respectively, whereas PreS2/S-transcript was significantly reduced in D5. Increased apoptotic cell death and marked upregulation in caspase-3/Bax/TNF-R1/FasR/TRAIL-R1/ROS/MCP-1/IP-10/MIP-1β expression were noticed specifically in D2- and also in D3-transfected cells, while D5 resulted in over-expression of ER-stress-markers. D-subgenotype-transfected Huh7 cells were co-cultured with PBMC of healthy-donors or LX-2 cells and significant increase in pro-inflammatory cytokines in PBMC and fibrogenic-markers in LX-2 were noticed in presence of D2/D3. Further, Huh7 cells transfected with D1, in particular and also D5, displayed remarkable induction of EMT-markers and high proliferative/migratory abilities. Collectively, our results demonstrated that D2/D3 were more associated with hepatic apoptosis/inflammation/fibrosis and D1/D5 with increased risk of hepatocarcinogenesis and emphasize the need for determining HBV-subgenotype in clinical practice.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-26414-4</identifier><identifier>PMID: 29795338</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/1 ; 13/109 ; 13/2 ; 13/31 ; 14/34 ; 14/63 ; 38/22 ; 38/23 ; 38/77 ; 38/90 ; 45/29 ; 631/326/596/1550 ; 692/420/254 ; 96/21 ; Antigens ; Apoptosis ; Caspase ; Caspase-3 ; Cell death ; Cloning ; Drug resistance ; Efficiency ; Fibrosis ; Genes ; Genomes ; Genotype & phenotype ; Genotypes ; Hepatitis B ; Humanities and Social Sciences ; Inflammation ; IP-10 protein ; Liver ; Liver diseases ; Medical education ; Monocyte chemoattractant protein 1 ; Monomers ; multidisciplinary ; Mutation ; Overexpression ; Peripheral blood mononuclear cells ; Science ; Science (multidisciplinary) ; Transcription ; Tumor necrosis factor</subject><ispartof>Scientific reports, 2018-05, Vol.8 (1), p.8055-11, Article 8055</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c523t-5d3f0fe3806e8aef3bca7769eaba0db4ed056a68144d37c5069b5347427948b33</citedby><cites>FETCH-LOGICAL-c523t-5d3f0fe3806e8aef3bca7769eaba0db4ed056a68144d37c5069b5347427948b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966457/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966457/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,27931,27932,41127,42196,51583,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29795338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khatun, Mousumi</creatorcontrib><creatorcontrib>Mondal, Rajiv Kumar</creatorcontrib><creatorcontrib>Pal, Sourina</creatorcontrib><creatorcontrib>Baidya, Ayana</creatorcontrib><creatorcontrib>Bishnu, Debasree</creatorcontrib><creatorcontrib>Banerjee, Priyanka</creatorcontrib><creatorcontrib>Santra, Amal Kumar</creatorcontrib><creatorcontrib>Dhali, Gopal Krishna</creatorcontrib><creatorcontrib>Banerjee, Soma</creatorcontrib><creatorcontrib>Chowdhury, Abhijit</creatorcontrib><creatorcontrib>Datta, Simanti</creatorcontrib><title>Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Distinct clinical features of HBV infection have been associated with different viral genotype/subgenotype. HBV Genotype-D comprised of 10 subgenotypes, D1–D10, whose clinical implications still remain elusive. We investigated for the first-time, the virologic characteristics and cytopathic effects of four non-recombinant D-subgenotypes, D1/D2/D3/D5. Expressions of viral/host genes were evaluated in Huh7 cells transfected with full-length, linear-monomers of HBV/D-subgenotypes or pGL3-Basic vector carrying subgenotype-specific HBx. Intracellular HBV-DNA and pregenomic-RNA levels were high in D1/D2 than D3/D5. Expressions of PreC-mRNA and HBx were highest for D2 and D1 respectively, whereas PreS2/S-transcript was significantly reduced in D5. Increased apoptotic cell death and marked upregulation in caspase-3/Bax/TNF-R1/FasR/TRAIL-R1/ROS/MCP-1/IP-10/MIP-1β expression were noticed specifically in D2- and also in D3-transfected cells, while D5 resulted in over-expression of ER-stress-markers. D-subgenotype-transfected Huh7 cells were co-cultured with PBMC of healthy-donors or LX-2 cells and significant increase in pro-inflammatory cytokines in PBMC and fibrogenic-markers in LX-2 were noticed in presence of D2/D3. Further, Huh7 cells transfected with D1, in particular and also D5, displayed remarkable induction of EMT-markers and high proliferative/migratory abilities. Collectively, our results demonstrated that D2/D3 were more associated with hepatic apoptosis/inflammation/fibrosis and D1/D5 with increased risk of hepatocarcinogenesis and emphasize the need for determining HBV-subgenotype in clinical practice.</description><subject>13</subject><subject>13/1</subject><subject>13/109</subject><subject>13/2</subject><subject>13/31</subject><subject>14/34</subject><subject>14/63</subject><subject>38/22</subject><subject>38/23</subject><subject>38/77</subject><subject>38/90</subject><subject>45/29</subject><subject>631/326/596/1550</subject><subject>692/420/254</subject><subject>96/21</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell death</subject><subject>Cloning</subject><subject>Drug resistance</subject><subject>Efficiency</subject><subject>Fibrosis</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genotype & 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Kumar ; Pal, Sourina ; Baidya, Ayana ; Bishnu, Debasree ; Banerjee, Priyanka ; Santra, Amal Kumar ; Dhali, Gopal Krishna ; Banerjee, Soma ; Chowdhury, Abhijit ; Datta, Simanti</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c523t-5d3f0fe3806e8aef3bca7769eaba0db4ed056a68144d37c5069b5347427948b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>13</topic><topic>13/1</topic><topic>13/109</topic><topic>13/2</topic><topic>13/31</topic><topic>14/34</topic><topic>14/63</topic><topic>38/22</topic><topic>38/23</topic><topic>38/77</topic><topic>38/90</topic><topic>45/29</topic><topic>631/326/596/1550</topic><topic>692/420/254</topic><topic>96/21</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell death</topic><topic>Cloning</topic><topic>Drug 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Simanti</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-05-23</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>8055</spage><epage>11</epage><pages>8055-11</pages><artnum>8055</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Distinct clinical features of HBV infection have been associated with different viral genotype/subgenotype. HBV Genotype-D comprised of 10 subgenotypes, D1–D10, whose clinical implications still remain elusive. We investigated for the first-time, the virologic characteristics and cytopathic effects of four non-recombinant D-subgenotypes, D1/D2/D3/D5. Expressions of viral/host genes were evaluated in Huh7 cells transfected with full-length, linear-monomers of HBV/D-subgenotypes or pGL3-Basic vector carrying subgenotype-specific HBx. Intracellular HBV-DNA and pregenomic-RNA levels were high in D1/D2 than D3/D5. Expressions of PreC-mRNA and HBx were highest for D2 and D1 respectively, whereas PreS2/S-transcript was significantly reduced in D5. Increased apoptotic cell death and marked upregulation in caspase-3/Bax/TNF-R1/FasR/TRAIL-R1/ROS/MCP-1/IP-10/MIP-1β expression were noticed specifically in D2- and also in D3-transfected cells, while D5 resulted in over-expression of ER-stress-markers. D-subgenotype-transfected Huh7 cells were co-cultured with PBMC of healthy-donors or LX-2 cells and significant increase in pro-inflammatory cytokines in PBMC and fibrogenic-markers in LX-2 were noticed in presence of D2/D3. Further, Huh7 cells transfected with D1, in particular and also D5, displayed remarkable induction of EMT-markers and high proliferative/migratory abilities. Collectively, our results demonstrated that D2/D3 were more associated with hepatic apoptosis/inflammation/fibrosis and D1/D5 with increased risk of hepatocarcinogenesis and emphasize the need for determining HBV-subgenotype in clinical practice.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29795338</pmid><doi>10.1038/s41598-018-26414-4</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13 13/1 13/109 13/2 13/31 14/34 14/63 38/22 38/23 38/77 38/90 45/29 631/326/596/1550 692/420/254 96/21 Antigens Apoptosis Caspase Caspase-3 Cell death Cloning Drug resistance Efficiency Fibrosis Genes Genomes Genotype & phenotype Genotypes Hepatitis B Humanities and Social Sciences Inflammation IP-10 protein Liver Liver diseases Medical education Monocyte chemoattractant protein 1 Monomers multidisciplinary Mutation Overexpression Peripheral blood mononuclear cells Science Science (multidisciplinary) Transcription Tumor necrosis factor |
| title | Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus |
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