5FNC1†Present address: Institute of Virology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 101, PR China.
5FNC2‡Present address: Functional Genomics of Drug Resistance, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, Li Ka-Shing Centre, Cambridge, UK.
Occult hepatitis B virus (HBV) infection (OBI), defined as the presence of HBV DNA without detectable HBV surface antigen (HBsAg), is frequent in west Africa, where genotype E is prevalent. The prevalence of OBI in 804 blood donors and 1368 pregnant women was 1.7 and 1.5 %, respectively. Nine of 32 OBI carriers were evaluated with HBV serology, viral load and complete HBV genome sequence of two to five clones. All samples except one were anti-HBV core antigen-positive and three contained antibodies against HBsAg (anti-HBs). All strains were of genotype E and formed quasispecies with 0.20–1.28 % intra-sample sequence variation. Few uncommon mutations (absent in 23 genotype E reference sequences) were found across the entire genome. Two mutations in the core region encoded truncated or abnormal capsid protein, potentially affecting viral production, but were probably rescued by non-mutated variants, as found in one clone. No evidence of escape mutants was found in anti-HBs-carrying samples, as the ‘a’ region was consistently wild type. OBI carriers constitute approximately 10 % of all HBV DNA-viraemic adult Ghanaians. OBI carriers appear as a disparate group, with a very low viral load in common, but multiple origins reflecting decades of natural evolution in an area essentially devoid of human intervention.
AllainJ.-P.,
CandottiD.,
SoldanK.,
SarkodieF.,
PhelpsB.,
GiachettiC.,
ShyamalaV.,
YeboahF.,
AnokwaM.other authors2003; The risk of hepatitis B virus infection by transfusion in Kumasi, Ghana. Blood 101:2419–2425[CrossRef]
BockC. T.,
MalekN. P.,
TillmannH. L.,
MannsM. P.,
TrautweinC.2000; The enhancer I core region contributes to the replication level of hepatitis B virus in vivo and in vitro. J Virol 74:2193–2202[CrossRef]
CandottiD.,
Opare-SemO.,
RezvanH.,
SarkodieF.,
AllainJ.-P.2006; Molecular and serological characterization of hepatitis B virus in deferred Ghanaian blood donors with and without elevated alanine amino transferase. J Viral Hepat 13:715–724[CrossRef]
CarmanW. F.,
BonerW.,
FattowichG.,
ColmanK.,
DornanE. S.,
ThurszM.,
HadziyannisS.1997; Hepatitis B virus core protein mutations are concentrated in B-cell epitopes in progressive disease and in T helper cell epitopes during clinical remission. J Infect Dis 175:1093–1100[CrossRef]
ErhardtA.,
ReinekeU.,
BlondinD.,
GerlichW. H.,
AdamsO.,
HeintgesT.,
NiederauC.,
HaussingerD.2000; Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B. Hepatology 31:716–725[CrossRef]
FujiwaraK.,
TanakaY.,
OritoE.,
OhnoT.,
KatoT.,
SugiharaK.,
HasegawaI.,
SakuraiM.,
ItoK.other authors2005; Distribution of HBV genotypes among HBV carriers in Benin: phylogenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol 11:6410–6415
FukaiK.,
TakadaS.,
YokosukaO.,
SaishoH.,
OmataM.,
KoikeK.1997; Characterization of a specific region in the hepatitis B virus enhancer I for the efficient expression of X gene in the hepatic cell. Virology 236:279–287[CrossRef]
GüntherS.,
PiwonN.,
JungA.,
IwanskaA.,
SchmitzH.,
WillH.2000; Enhanced replication contributes to enrichment of hepatitis B virus with a deletion in the core gene. Virology 273:286–299[CrossRef]
Ha-LeeY. M.,
LeeJ.,
PyunH.,
KimY.,
SohnJ.,
ChoY. J.,
KimY.2001; Sequence variations of hepatitis B promoter regions in persistently infected patients. Arch Virol 146:279–292[CrossRef]
HattonT.,
ZhouS.,
StandringD. N.1992; RNA- and DNA-binding activities in hepatitis B virus capsid protein: a model for their roles in viral replication. J Virol 66:5232–5241
HuyT. T.,
IshikawaK.,
AmpofoW.,
IzumiT.,
NakajimaA.,
AnsahJ.,
TettehJ. O.,
Nii-TrebiN.,
AidooS.other authors2006; Characteristics of hepatitis B virus in Ghana: full length genome sequences indicate the endemicity of genotype E in West Africa. J Med Virol 78:178–184[CrossRef]
JeantetD.,
CheminI.,
MandrandB.,
ZoulimF.,
TrepoC.,
KayA.2002; Characterization of two hepatitis B virus populations isolated from a hepatitis B surface antigen-negative patient. Hepatology 35:1215–1224[CrossRef]
KremsdorfD.,
GarreauF.,
DuclosH.,
ThiersV.,
SchellekensH.,
PetitM. A.,
BrechotC.1993; Complete nucleotide sequence and viral envelope protein expression of a hepatitis B virus DNA derived from a hepatitis B surface antigen-seronegative patient. J Hepatol 18:244–250[CrossRef]
LiaoW.,
OuJ. H.1995; Phosphorylation and nuclear localization of the hepatitis B virus core protein: significance of serine in the three repeated SPRRR motifs. J Virol 69:1025–1029
MirnyL. A.,
ShakhnovichE. I.1999; Universally conserved positions in protein folds: reading evolutionary signals about stability, folding kinetics and function. J Mol Biol 291:177–196[CrossRef]
NassalM.1992; The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol 66:4107–4116
NeurathA. R.,
KentS. B.,
StrickN.,
ParkerK.1986; Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell 46:429–436[CrossRef]
PetitM. A.,
DubanchetS.,
CapelF.,
VoetP.,
DauguetC.,
HauserP.1991; HepG2 cell binding activities of different hepatitis B virus isolates: inhibitory effect of anti-HBs and anti-preS1(21–47). Virology 180:483–491[CrossRef]
PochO.,
SauvagetI.,
DelarueM.,
TordoN.1989; Identification of four conserved motifs among the RNA-dependent polymerase encoding elements. EMBO J 8:3867–3874
PontissoP.,
RuvolettoM. G.,
GerlichW. H.,
HeermannK. H.,
BardiniR.,
AlbertiA.1989; Identification of an attachment site for human liver plasma membranes on hepatitis B virus particles. Virology 173:522–530[CrossRef]
RadziwillG.,
TuckerW.,
SchallerH.1990; Mutational analysis of the hepatitis B virus P gene product: domain structure and RNase H activity. J Virol 64:613–620
RaneyA. K.,
LeH. B.,
McLachlanA.1992; Regulation of transcription from the hepatitis B virus major surface antigen promoter by the Sp1 transcription factor. J Virol 66:6912–6921
RehermannB.,
FerrariC.,
PasquinelliC.,
ChisariF. V.1996; The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med 2:1104–1108[CrossRef]
RosemanA. M.,
BerrimanJ. A.,
WynneS. A.,
ButlerP. J.,
CrowtherR. A.2005; A structural model for maturation of the hepatitis B virus core. Proc Natl Acad Sci U S A 102:15821–15826[CrossRef]
SchoriesM.,
PetersT.,
RasenackJ.2000; Isolation, characterization and biological significance of hepatitis B virus mutants from serum of a patient with immunologically negative HBV infection. J Hepatol 33:799–811[CrossRef]
ShaulY.,
Ben-LevyR.,
De-MedinaT.1986; High affinity binding site for nuclear factor I next to the hepatitis B virus S gene promoter. EMBO J 5:1967–1971
SwoffordD. L.,
SullivanJ.2003; Phylogenetic inference based on parsimony and other methods using paup*. In The Phylogenetic Handbook: A Practical Approach to DNA and Protein Phylogeny . pp 160–196Edited bySalemiM.,
VandammeA.-M.
Cambridge: Cambridge University Press;
UchidaT.,
ShimojimaS.,
GotohK.,
ShikataT.,
MimaS.1994; Pathology of livers infected with “silent” hepatitis B virus mutant. Liver 14:251–256
UchidaT.,
GotohK.,
ShikataT.1995; Complete nucleotide sequences and the characteristics of two hepatitis B virus mutants causing serologically negative acute or chronic hepatitis B. J Med Virol 45:247–252[CrossRef]
WeinbergerK. M.,
WiedenmannE.,
BohmS.,
JilgW.2000; Sensitive and accurate quantitation of hepatitis B virus DNA using kinetic fluorescence detection system (TaqMan PCR). J Virol Methods 85:75–82[CrossRef]