Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus

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.

On-treatment monitoring of liver fibrosis with serum hepatitis B core-related antigen in chronic hepatitis B

“…Our data showed that serum HBcrAg level was significantly associated with younger age, HBeAg positivity, higher HBV-DNA titers, and high qHBsAg level, but not HBV genotypes. As noted earlier, the HBV genotype might depend on the biogeography, and not be affected by any host or viral proteins, but can influence the progression of liver disease[33-35]. Our results confirmed that there was no independent association between HBV genotype and serum HBcrAg level, indicating that HBV-triggered liver injury is mediated by host immune response to viral proteins[33].…”

“…As noted earlier, the HBV genotype might depend on the biogeography, and not be affected by any host or viral proteins, but can influence the progression of liver disease[33-35]. Our results confirmed that there was no independent association between HBV genotype and serum HBcrAg level, indicating that HBV-triggered liver injury is mediated by host immune response to viral proteins[33]. Interestingly, we found that patients with BCP/PC mutation had a significantly lower serum concentration of HBcrAg when compared with their wild-type counterparts.…”

Okült Hepati̇t B Vi̇rüsünün Genoti̇p, Subgenoti̇p Ve Subti̇p Anali̇zi̇

“…Serum örnekleri: Biyopsi örnekleri ile eş zamanlı ve normal kan alma (venöz) prosedürü uyarınca uygun tüplere alınan hasta kan örnekleri santrifüj edilerek serumları ayrıldıktan sonra steril ependorf tüplere transfer edilerek laboratuar çalışmaları için -80 • C'de muhafaza edilmiştir. HBV/D'nin çoklu coğrafik yayılım ve yüksek heterojenite içeren genotiplerden biri olması, daha yüksek oranda S gen mutasyon/varyasyon içermesi, HBV/D3'ün OBI'li bireylerde diğer subgenotiplere oranla daha fazla varyasyon içerdiği, kronik hepatit B hastaları arasında ise diğer subgenotiplere oranla daha az HBV DNA yükü, daha yavaş hastalık progresyonu ve daha düşük onkojenik potansiyel ile daha düşük replikasyon kapasitesi ile karakterize olduğu yönündeki veriler bu yaklaşımı destekler niteliktedir (30)(31)(32). HBV/D3 subgenotopinin bazı coğrafik bölgelerde HBsAg seronegatif kan donörleri ile OBI için risk faktörü olarak kabul edilen damar içi uyuşturucu kullananlar ve madde bağımlıları ile HIV ile ko-enfekte OBI vakalarında daha sık tespit edildiğine dair veriler de HBV/ D3'ün OBI ile ilişkili olabileceğine işaret etmektedir (33).…”

Persistence of Hepatitis B Virus Infection: A Multi-Faceted Player for Hepatocarcinogenesis

“…One study with Alaskan natives reported that genotype C2 and F develop HCC more than genotype A2, B6, and D ( McMahon, 2009 ). In India, subgenotypes D1 and D3 have been found to be associated with advanced diseases though D2 showed highest replication efficiency ( Datta et al, 2018 ; Khatun et al, 2018 ). Although genotype D has been reported as an independent risk factor for fulminant hepatitis ( Thukar et al, 2002 ; Wai et al, 2005 ), genotype G is rarely seen alone.…”