Biomedical subjects

Anna Kramvis

Publications and source records attributed to Anna Kramvis.

18 recordsLinked to original sources

PubMed2006

Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens.

Various genotypes of the hepatitis B virus (HBV) induce liver disease of distinct severity, but the underlying virological differences are not well defined. Huh7 cells were transfected with plasmids carrying 1.24-fold the HBV genome of different genotypes/subgenotypes (2 strains each for Aa/A1, Ae/A2, Ba/B2 and D; 3 each for Bj/B1 and C). HBV DNA levels in cell lysates, determined by Southern hybridization, were the highest for C followed by Bj/Ba and D/Ae (P < .01), and the lowest for Aa (P < .01), whereas in culture media, they were the highest for Bj, distantly followed by Ba/C/D and further by Ae/Aa (P < .01). The intracellular expression of core protein was more than 3-fold lower for Ae/Aa than the others. Hepatitis B e antigen (HBeAg) was excreted in a trend similar to that of HBV DNA with smaller differences. Secretion of hepatitis B surface antigen (HBsAg) was most abundant for Ae followed by Aa, Ba, Bj/C and remotely by D, which was consistent with mRNA levels. Cellular stress determined by the reporter assay for Grp78 promoter was higher for C and Ba than the other genotypes/subgenotypes (P < .01). Severe combined immunodeficiency mice transgenic for urokinase-type plasminogen activator (uPA/SCID), with the liver replaced for human hepatocytes, were inoculated with virions passed in mouse and recovered from culture supernatants. HBV DNA levels in their sera were higher for C than Ae by 2 logs during 4-7 weeks after inoculation. In conclusion, virological differences among HBV genotypes were demonstrated both in vitro and in vivo. These differences may influence HBV infections with distinct genotypes in clinical and epidemiological settings.

Adolescent↗

PubMed2006

Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality.

BACKGROUND & AIMS: Molecular evolutionary analysis based on coalescent theory can provide important insights into epidemiologic processes worldwide. This approach was combined with analyses of the hepatitis C virus (HCV) epidemiologic-historical background and HCV-related hepatocellular carcinoma (HCC) in different countries. METHODS: The HCV gene sequences of 131 genotype 1b (HCV-1b) strains from Japan, 38 HCV-1a strains from the United States, 33 HCV-1b strains from Spain, 27 HCV-3a strains from the former Soviet Union (FSU), 47 HCV-4a strains from Egypt, 25 HCV-5a strains from South Africa, and 24 HCV-6a strains from Hong Kong isolated in this study and previous studies were analyzed. RESULTS: The coalescent analysis indicated that a transition from constant size to rapid exponential growth (spread time) occurred in Japan in the 1920s (HCV-1b), but not until the 1940s for the same genotype in Spain and other European countries. The spread time of HCV-1a in the United States was estimated to be in the 1960s; HCV-3a in the FSU, HCV-5a in South Africa, and HCV-6a in Hong Kong in the 1960s, mid-1950s, and late 1970s, respectively. Three different linear progression curves were determined by analysis of the relationship between HCV seroprevalence and HCC mortality in different geographic regions; a steep ascent indicated the greatest progression to HCC in Japan, a near horizontal line indicated the least progression in the United States and the FSU, and an intermediate slope was observed in Europe. CONCLUSIONS: These findings strongly suggest that the initial spread time of HCV is associated with the progression dynamics of HCC in each area, irrespective of genotype.

Adult↗

PubMed2006

Immune suppression uncovers endogenous cytopathic effects of the hepatitis B virus.

It is generally accepted that the host's immune response rather than the virus itself is causing the hepatocellular damage seen in acute and chronic hepatitis B virus (HBV) infections. However, in situations of severe immune suppression, chronic HBV patients may develop a considerable degree of liver disease. To examine whether HBV has direct cytopathic effects in severely immune compromised hosts, we have infected severe combined immune deficient mice (uPA-SCID), harboring human liver cells, with HBV. Serologic analysis of the plasma of HBV-infected animals revealed the presence of extremely high amounts of viral genomes and proteins. Histological analysis of the livers of uPA-SCID chimeras infected with HBV for more than 2 months showed that the majority of human hepatocytes had a ground-glass appearance, stained intensely for viral proteins, and showed signs of considerable damage and cell death. This histopathologic pattern closely resembles the picture observed in the livers of immunosuppressed HBV patients. These lesions were not observed in animals infected with HBV for less than 1 month. Ultrastructural analysis of long-term-infected hepatocytes showed a highly increased presence of cylindrical HBsAg structures, core particles, and Dane particles compared to short-term-infected hepatocytes. These long-term-infected hepatocytes also contained elevated amounts of HBV cccDNA. In conclusion, HBV causes dramatic intracellular changes and hepatocellular damage in the human hepatocytes that reside in a severely immune deficient mouse. These lesions show much resemblance to the ones encountered in immunosuppressed chronic HBV patients. Our observations indicate that HBV may be directly cytopathic in conditions of severe immune suppression.

Animals↗

PubMed2005

Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B.

AIM: To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation. METHODS: DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced. RESULTS: HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1,774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time. CONCLUSION: Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.

Acute Disease↗

PubMed2005

Hepatitis B virus genotypes.

Eight genotypes of hepatitis B virus (A-H) are currently recognized, and subgenotypes have recently been described in four of these genotypes (A, B, C and F). The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus. Structural and functional differences between genotypes can influence the severity, course and likelihood of complications, and response to treatment of hepatitis B virus infection and possibly vaccination against the virus. Although the number of studies on these genotypes has increased dramatically during recent years, much remains to be learnt about their full implications.

Animals↗

PubMed2005

Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans.

Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern Africa, with genotype A predominating. Their hepatocarcinogenic potential in Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control format, we investigated the hepatocarcinogenic potential of these genotypes and subgenotype A1 of genotype A, which accounts for the great majority of genotype A isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans with hepatocellular carcinoma (HCC) and 111 matched asymptomatic chronic carriers, serving as controls, were genotyped using the method of [Lindh et al. (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined using an in-house restriction fragment length polymorphism assay. Genotype A was present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers infected with genotype A compared with those infected with non-A genotypes. HCC patients infected with genotype A were significantly younger than those infected with non-A genotypes (P = 0.02). The distributions between these two groups according to sex, geographic background, and tribe were not significantly different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of 70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits: 1.73,10.23) of HCC in those infected with subgenotype A1 compared with those infected with non-A genotypes. Genotype A has a greater hepatocarcinogenic potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is entirely attributable to subgenotype A1.

Adolescent↗

PubMed2005

Full genome analysis of hepatitis B virus genotype E strains from South-Western Africa and Madagascar reveals low genetic variability.

The eight genotypes of hepatitis B virus (HBV), A-H, have a characteristic geographical distribution. The high prevalence of genotype E within a wide expanse of Africa makes it important to characterize this genotype. Although the preS/S region of a large number of genotype E isolates has been sequenced, to date only eight complete genotype E genomes have been published. The aim of this study, therefore, was to sequence and characterize the complete genome of genotype E isolates obtained from geographically distinct regions in Africa, including Namibia, Angola, and Madagascar. The nine newly sequenced genotype E isolates were closely related with an intra-group nucleotide divergence of 1.2%, reflecting their close geographical origin. All genotype E strains have the same characteristics, an in-frame deletion of three nucleotides (one amino acid) in the 5' pre-S1, a signature pattern of amino acids in the pre-S1 region and the serological subtype ayw4. In addition, we have identified another unique attribute of genotype E strains, the introduction of another start codon Met(83) in the pre-S1 region that may result in the translation of an elongated middle hepatitis B surface protein (MHBs).

Adult↗

PubMed2004

A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D.

There are two subtypes of hepatitis B virus genotype A (HBV/A) and they are provisionally designated Aa ("a" standing for Africa/Asia) and Ae ("e" for Europe). In a case-control study, 78 HBV/Aa, 78HBV/Ae, and 78HBV/D carriers from several countries were compared. The prevalence of HBe antigen (HBeAg) in serum was significantly lower in carriers of HBV/Aa than in carriers of HBV/Ae (31% vs. 49%; P = .033), with a difference more obvious in the carriers aged 30 years or younger (34% vs. 67%; P = .029). HBV DNA levels in the carriers of HBV/Aa (median, 3.46 log copies/mL; 95% CI, 2.93-3.95) were significantly lower than those of carriers of HBV/Ae (6.09 log copies/mL; 95% CI, 4.24-7.64) or of carriers of HBV/D (5.48 log copies/mL; 95% CI, 4.06-7.02), regardless of the HBeAg status (P < .001). The most specific and frequent substitutions in 54 HBV/Aa isolates were double substitutions for T1809 (100%) and T1812 (96%) immediately upstream of the precore initiation codon, which would interfere with the translation of HBeAg in HBV/Aa infections. They were not detected in 57 HBV/Ae or 61 HBV/D isolates examined. The double mutation in the core promoter (T1762/A1764) was more frequent in both HBV/Aa (50%) and HBV/Ae (44%) than in HBV/D isolates (25%; P < .01), whereas the precore mutation (A1896) occurred in HBV/D isolates only (48%; P < .0001). In conclusion, the clearance of HBeAg from serum may occur by different mechanisms in HBV/Aa, HBV/Ae, and HBV/D infections, which may influence clinical manifestations in the Western countries where both genotypes A and D are prevalent.

Base Sequence↗

PubMed2004

Molecular characterization of duck hepatitis B virus isolates from South African ducks.

The objective of the study was to characterize the genome of duck hepatitis B virus (DHBV) isolates from South African Pekin ducks. Duck serum and liver samples were collected from two commercial duck farms from geographically distinct regions of South Africa. In total, 498 duck serum samples were tested for the presence of DHBV DNA using either sub-genomic or full-length polymerase chain reaction (PCR) assays. The overall prevalence of DHBV infection in South African ducks was 47%. In addition, 30% of 59 liver tissues tested were DHBV DNA-positive. Six randomly selected serum or liver samples were used to clone and sequence the genomes of the South African DHBV strains. All six isolates had DHBV genomes of 3,021 nucleotides with three characteristic overlapping reading frames encoding the polymerase, surface and core gene products. No X-like gene with a traditional start codon was found. Following phylogenetic analysis, the South African DHBV isolates clustered with DHBV isolates from other "Western" countries, including United States of America, Canada, Germany and India. On translation of the open reading frames, the South African isolates were found to share signature amino acids in the polymerase and surface genes with the "Western" country isolates as opposed to those of Chinese DHBV isolates.

Animals↗

PubMed2004

Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa.

Phylogenetic analysis of hepatitis B virus (HBV) has led to its classification into eight genotypes, A to H. The dominant genotype in South Africa is genotype A, which consists of two subgenotypes, A1 and A2. Subgenotype A1 (previously subgroup A') predominates over subgenotype A2 (previously subgroup A minus A'). The complete genome of HBV isolated from 18 asymptomatic carriers of the virus and five acute hepatitis B patients was amplified; the resulting amplicons were cloned and sequenced. All acute hepatitis isolates belonged to subgenotype A1 and had no distinguishing mutations relative to the isolates from asymptomatic carriers, which had a distribution of ten subgenotype A1, two subgenotype A2 and six genotype D. The presence of the previously described amino acid residues that distinguish subgenotype A1 (subgroup A') from the remainder of genotype A in the S and polymerase genes was confirmed. Moreover, the large number of subgenotype A1 isolates sequenced allowed identification in the other open reading frames of additional nucleotide and amino acid changes that are characteristic of subgenotype A1. In particular, nucleotide mutations at positions 1809-1812 that alter the Kozak sequence of the precore/core open reading frame, and A(1888) in the precore region, were found exclusively in subgenotype A1 isolates. Unique sequence alterations of the transcriptional regulatory elements were also found in subgenotype A1 isolates. The mean nucleotide divergence of subgenotype A1 was greater than that of subgenotype A2, suggesting that this subgenotype has been endemic for a longer time in the South African black population than had subgenotype A2.

Carrier State↗

PubMed2004

Novel hepatitis B virus genotype a subtyping assay that distinguishes subtype Aa from Ae and its application in epidemiological studies.

The eight genotypes of hepatitis B virus (HBV) have different geographical distributions, virological characteristics, and clinical manifestations. A unique subtype of HBV genotype A (HBV/A) was reported in sub-Saharan Africa, raising the possibility that patients infected with this subtype (HBV/Aa ["a" for African and Asian]) may have different clinical outcomes than other HBV/A isolates (HBV/Ae ["e" for European]). Comparison between 30 HBV/Aa and 30 HBV/Ae isolates indicated that almost all HBV/Ae isolates had G at nucleotide (nt) 1809 and C at nt 1812, whereas HBV/Aa isolates had T1809/T1812. Taking advantage of these two single nucleotide polymorphisms (SNPs), a novel subtype-specific PCR assay in the X/precore/core region was developed. This assay was combined with a restriction fragment length polymorphism assay using BglII in a different region (nt 1984 to 1989), which has a SNP distinguishing HBV/Aa from HBV/Ae, resulting in 100% specificity for the combined assay. Application of the subtyping assay using sera from 109 paid donors in the United States indicated significantly different distributions of HBV/A subtypes among races; African-Americans, Caucasians, and Hispanics had HBV/Ae, whereas Asians had mainly HBV/Aa, suggesting that the HBV/Aa isolates may have been imported by recent immigration from Asia. In conclusion, the specificity and sensitivity of the combined subtyping assay were confirmed, and its usefulness was demonstrated in a practical context.

Adolescent↗

PubMed2003

Frequent coinfection with hepatitis B virus strains of distinct genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support.

A genotype-specific probes assay (GSPA) was developed for distinguishing the seven genotypes (A-G) of hepatitis B virus (HBV). Nucleotide (nt) sequences corresponding to preS1 region were amplified by PCR with a primer labeled with biotin, and delivered to eight wells on which complementary sequences specific to one or other genotype had been immobilized. Thereafter, hybridization of HBV DNA sequences amplified from the test serum was detected by colorimetry. When 256 sera from HBV carriers in Bangladesh, Cameroon, Japan, South Africa, USA and Uzbekistan were subjected to GSPA, genotypes were concordant with those of ELISA with monoclonal antibodies to epitopes on preS2-region products in 242 (94.6%) of them; 8 sera (3.1%) were not genotypeable by either method. Cloning analysis confirmed the presence of two distinct HBV genotypes in the seven selected sera with coinfection. There were 7 (2.7%) sera with discordant genotyping results between GSPA and ELISA. When HBV DNA clones propagated from these sera were sequenced and analyzed phylogenetically, the genotypes determined by GSPA were verified. Coinfection with HBV strains of two distinct genotypes was identified by GSPA in 28 (10.9%) sera, while it was suggested by ELISA in only 2 (0.8%) sera. The GSPA method would be particularly useful for detecting the coinfection with distinct HBV genotypes of any clinical relevance, which seems to be more frequent than reported previously.

Biotin↗

PubMed2003

Sequence variation upstream of precore translation initiation codon reduces hepatitis B virus e antigen production.

BACKGROUND & AIMS: Most South African hepatitis B virus strains harbor point mutations immediately upstream of the precore AUG codon. The aim of this study was to determine their effect on hepatitis B e antigen expression. METHODS: The hepatitis B virus DNA sequence around the precore region was determined from sera of 45 black South Africans. The South African mutations were introduced into hepatitis B virus dimers of the same genotype, and hepatitis B e antigen was quantified from culture medium of transfected HepG2 or Huh7 cells. RESULTS: The South African sequence changes were easily detectable in the acute, hepatitis B e antigen-positive phase of infection, suggesting that they were stable traits and were not selected by immune pressure. Triple mutations at the -5, -3, and -2 positions of the AUG codon severely impaired hepatitis B e antigen expression (P < 0.001). The frequent double mutation at the -5 and -2 positions moderately reduced hepatitis B e antigen levels (P < 0.001) to an extent comparable to that of the common core promoter mutations (1762(T)1764(A)). The presence of both South African and core promoter mutations diminished hepatitis B e antigen expression in an additive manner. It is interesting to note that the triple South African mutations enabled core protein translation from precore messenger RNA, which could rescue the replication defect of a hepatitis B virus genome with an ablated core gene. CONCLUSIONS: We have identified a novel class of hepatitis B e antigen variants with reduced hepatitis B e antigen translation by a ribosomal leaky scanning mechanism. Reduction in hepatitis B e antigen expression may contribute to accelerated seroconversion from hepatitis B e antigen to its antibody in black South Africans infected with hepatitis B virus very early in life.

Adolescent↗

PubMed2003

Follow up of infection of chacma baboons with inoculum containing A and non-A genotypes of hepatitis B virus.

AIM: To determine whether one genotype (A or non-A genotypes of HBV) predominated over the other during the course of HBV infection. METHODS: Four baboons were inoculated with HBV. DNA was extracted from serum obtained at monthly intervals post-inoculation for 52 weeks and HBV DNA was amplified using primers specific for the core region containing an insert characteristic of genotype A (nt 2 354-2 359, numbering from the EcoRI site). The amplicons were cloned into PCR-Script(TM) and a minimum of 15 clones per time point were sequenced in both directions. RESULTS: Both genotypes persisted for the entire follow-up period of 52 weeks. Genotype non-A predominated in two baboons and genotype A in one baboon. Neither genotype predominated in the fourth baboon, as shown at a 5 % level of testing. CONCLUSION: No conclusions concerning the dominance of either genotype or the natural progression or replication rates of HBV could be drawn because the pattern of the genotypes found may have been caused by sampling fluctuations at the time of DNA extraction and cloning as a result of the very low viral loads in the baboon sera.

Animals↗

PubMed2002

HLA associations with HBV carriage and proteinuria.

Human leucocyte antigen (HLA) associations have been reported in children with hepatitis B virus (HBV) associated membranous nephropathy (MN). In a previous study, we found an association with HLA DQB1*0603 in black children with HBVMN. To determine whether HLA DQB1*0603 predisposes to HBV carriage and development of abnormal proteinuria, we studied 70 family members of 14 children with HBVMN positive for HLA DQB1*0603. HBV was determined using third generation ELISA, slot-blot hybridisation, and nested polymerase chain reaction. HLA class I antigens were determined using a two-staged lymphocytotoxic test whereas class II antigen typing was done using sequence-specific primers. Abnormal proteinuria was defined by a protein/creatinine ratio > or =0.2. Associations of HLA DQB1*0603 with HBV carriage and abnormal proteinuria were determined using the mean probability ratio (LOD scores). Forty-seven (67%) family members were positive for HBV infection. Nineteen (27%) had abnormal range proteinuria. LOD scores in the study subjects with DQB1*0603 who were HBV negative versus those with DQB1*0603 who were HBV positive was not significant (anti-log sum =2.0559 and average 0.23). When a similar calculation was made for abnormal proteinuria, there were no significant findings (anti-log sum =3.8587 and average 0.43). This lack of association of HLA DQB1*0603 with either HBV carriage or abnormal proteinuria in family members suggests that additional factors may play a role in predisposing children to chronic HBV carriage and the development of MN. We therefore conclude that the main effect of HLA DQB1*0603 that distinguishes family members from HBVMN is the degree of proteinuria, which is a reflection of the severity of glomerular basement membrane damage in the latter.

Adolescent↗

PubMed2002

Hepatitis B and C virus co-infection in black children with membranous nephropathy.

Membranous glomerulonephritis is a recognized complication of hepatitis B virus infection, especially in children, and an occasional complication of hepatitis C virus infection. Co-infection with the two viruses has not previously been described in membranous glomerulonephritis. We report five black African children with membranous glomerulonephritis who were co-infected with hepatitis B and C viruses. Proof of hepatitis B virus infection was obtained using serological and molecular detection methods. Hepatitis C virus infection was demonstrated using reverse transcription to convert viral RNA to cDNA followed by amplification of the cDNA using a double round of the polymerase chain reaction with confirmation by Southern hybridization and nucleotide sequencing. The clinical, biochemical, immunological, and pathological characteristics of the co-infected children, as well as the natural history of the disease, did not differ from those in 24 children with hepatitis B virus-associated membranous glomerulonephritis. Of the 24 family and household contacts of the five co-infected children, 7 were infected with hepatitis B virus, 1 with hepatitis C virus, and none with both viruses. It is not known whether infection with the two viruses was acquired simultaneously or sequentially. Thus, black children with membranous glomerulonephritis are occasionally co-infected with hepatitis B and C viruses. The resulting disease appears to be no more severe than that in children infected with hepatitis B virus alone.

Adolescent↗

PubMed2002

Treatment of hepatitis B virus-associated nephropathy in black children.

The efficacy of interferon (IFN) in the treatment of hepatitis B virus (HBV)-associated nephropathy in black children has not been established. Twenty-four black children with biopsy-proven HBV-associated nephropathy were recruited into the study during the period April 1997 to June 1999. Five defaulted treatment and were excluded from the primary analysis. IFNalpha 2b was administered for 16 weeks. Response to treatment was defined as loss of HBeAg, decrease in proteinuria, and prevention of deterioration in renal and liver function. A control group of 20 patients was followed up for the same period. Ten (52.6%) of the treated children responded with clearance of HBeAg by 40 weeks. None cleared HBsAg. All responders showed remission of proteinuria, 90% maintained normal renal function and 1 (10%) showed improvement of renal function. HBV DNA levels decreased in this group. Nine patients did not clear HBeAg; none showed remission of proteinuria, and two showed deterioration of renal function. Liver enzymes rose during treatment but subsequently declined irrespective of response to therapy. No serious side effects were encountered. Only 5% of controls showed spontaneous clearance of HBeAg, and none had remission of proteinuria. Black children with HBV-associated nephropathy show accelerated clearance of HBeAg with remission of proteinuria following treatment with IFNalpha 2b. IFNalpha 2b was well tolerated.

Adolescent↗

PubMed2002

Analysis of the complete genome of subgroup A' hepatitis B virus isolates from South Africa.

A phylogenetic analysis is presented of six complete and seven pre-S1/S2/S gene sequences of hepatitis B virus (HBV) isolates from South Africa. Five of the full-length sequences and all of the pre-S2/S sequences have been previously reported. Four of the six complete genomes and three of the five incomplete sequences clustered with subgroup A', a unique segment of genotype A of HBV previously identified in 60% of South African isolates using analysis of the pre-S2/S region alone. This separation was also evident when the polymerase open reading frame was analysed, but not on analysis of either the X or pre-core/core genes. Amino acids were identified in the pre-S1 and polymerase regions specific to subgroup A'. In common with genotype D, 10 of 11 genotype A South African isolates had an 11 amino acid deletion in the amino end of the pre-S1 region. This deletion is also found in hepadnaviruses from non-human primates.

Base Sequence↗