Hepatitis B Virus DNA Splicing in Lebanese Blood Donors and Genotype A to E Strains: Implications for Hepatitis B Virus DNA Quantification and Infectivity

Abstract

Hepatitis B virus (HBV) is one of the major viruses transmissible by blood that causes chronic infection in immunocompromised individuals. The study of 61 HBV carrier blood donors from Lebanon revealed multiple patterns of spliced HBV DNA. HBV DNA splicing was examined and quantified in samples of five genotypes and in seroconversion panels. The Lebanese sample median viral load was 1.5 ×10 2 IU/ml. All strains were genotype D, serotype ayw; 35 clustered as subgenotype D1 and 7 clustered as subgenotype D2. Three splice variants (SP1, SP1A, and Pol/S) were observed in 12 high-viral-load samples. Twenty samples of each genotype, A to E, were tested for the presence of HBV spliced DNA and SP1-specific splice variant. An unspliced HBV genome was dominant, but 100% of strains with a viral load of ≥10 5 copies/ml contained various proportions of spliced DNA. SP1 was detected in 56/100 (56%) samples in levels that correlated with the overall viral load. HBV DNA quantification with S (unspliced) and X (total DNA) regions provided different levels of viral load, with the difference corresponding to spliced DNA. During the highly infectious window period, the SP1 variant became detectable shortly after the hepatitis B surface antigen (HBsAg), suggesting a correlation between the initiation of splicing and the production of detectable levels of HBsAg. The quantification of HBV DNA with primers located outside and inside the spliced region might provide different estimations of viral load and differentiate between infectious and defective viral genomes. The role of splicing neoproteins in HBV replication and interaction with the host remains to be determined.

Molecular and Immunological Study of Hepatitis B virus infection in Samara City, Iraq.

“…This is consistent with others who reported predominance of D genotype in the studies performed in Arab countries that included females only [13][14][15][16][17][18][19][20][21].…”

“…In Mosul, Iraq, Shafiq [12] [2013] reported that genotype D is the predominant genotype in HBV acute and chronic infections. In addition, another study found that D genotype is the predominant among Mosul blood donors [11].In Arab countries the predominant genotype was D in Saudi Arabia [13], United Arab Emirates [14], Yemen [15], Lebanon [16], Jordan [17], Egypt [25], Libya [18] Mauritania [19], Morocco [20], and Syria [21].…”

Low Prevalence of Occult Hepatitis B Infection Among Blood Donors in Beirut, Lebanon: Reconsider the Deferral Strategy of Anti-HBc Positive Blood Donors

“…In a previous study conducted between July 2009 and January 2011, 61 HBsAg positive donors were tested for NAT (35) and when compared to the current study, 21 HBsAg were positive. Both of studies have a comparable distribution of HBV viral load at 2 different periods of time, with a predominance of a low viral load in anti-HBe positive, asymptomatic, blood donors (Figure 1).…”

“…3 Chaar et al previously sequenced 42 HBV full genome strains isolated from Lebanon and demonstrated that genotype D strains were the only circulating viruses; in addition various mutations were found in the S and core genes, those were associated with escape detection or disruption of protein synthesis (35,39,40) In this study, the prevalence of OBI in healthy anti-HBc seropositive blood donors was 0.3% (n = 1/341), only 1 Syrian donor was an OBI carrier with a high anti HBs level > 1000 mIU/mL. Molecular analysis for the detection of any mutation associated with the occult strain was not studied due to plasma volume limitation.…”

Hepatitis B and C virus infections among pregnant women in Arab and African countries

“…D is the most common genotype among the different settings throughout the previously mentioned Arab states [37][38][39][40][41][42][43][44][45][46].…”