- Volume 83, Issue 9, 2002

It was observed recently that recombinant yeast-derived hepatitis B surface antigen (rHBsAg) particles, which contain the S protein only, bind almost exclusively to monocytes. It is shown here that binding requires the presence of the LPS receptor CD14. Furthermore, evidence is presented that a domain on CD14 that is identical to or largely overlaps with the LPS-binding pocket is instrumental for the attachment of rHBsAg. Additionally, it is shown that the heat-labile LPS-binding protein (LBP) catalyses the binding of rHBsAg to the cells. Remarkably, natural plasma-derived HBsAg (pHBsAg) does not have this property. pHBsAg devoid of its lipids and reconstituted with phosphatidylserine or phosphatidylglycerol acquires the characteristic of yeast-derived HBsAg. Clearly, the interaction of rHBsAg with the cell membrane is determined by the presence of charged phospholipids that are absent in pHBsAg. Although a lipid–receptor interaction is suggested, antibody-inhibition experiments suggest a possible involvement of the C-terminal region of the S protein in the interaction with monocytes. The possible implications of these observations for hepatitis B virus (HBV) infection and HBV vaccine efficiency are discussed.

The prevalence of a G1862T variant of hepatitis B virus (HBV) has been investigated in patients with fulminant hepatitis and chronic liver disease, using primer mismatch amplification, followed by restriction fragment length polymorphism analysis. This variant was five times more common in patients with fulminant hepatitis (13·7%, 7 of 52) than in chronic carriers (2·5%, 2 of 81). The G→T substitution at position 1862 leads to an amino acid change in codon 17 of the precore protein of the virus, which is part of a signal peptidase recognition motif. Variants with this mutation were only seen in patients infected with genotype B. In vitro translation experiments showed that this variant has greatly reduced capacity to produce hepatitis B e antigen (HBeAg) from its precore protein precursor. Furthermore, 88·5% of patients with fulminant hepatitis had mutations that are known to be associated with abrogated or reduced production of HBeAg. This suggests that, following HBV infection, the absence or reduced amounts of HBeAg may be a contributing factor in fulminant disease.

In the canine oral papillomavirus (COPV) model, following wart regression, COPV DNA was detected by PCR at the challenge site. However, following particle-mediated immunotherapeutic delivery (PMID) of COPV L1 and subsequent challenge, no COPV DNA could be detected. These data support PMID of COPV L1 as a protective vaccine and suggest that PMID of L1 may induce virus clearance.

We have characterized the complete genome (8300 bp) of an isolate of Felis domesticus papillomavirus (FdPV) from a domestic cat with cutaneous papillomatosis. A BLAST homology search using the nucleotide sequence of the L1 open reading frame demonstrated that the FdPV genome was most closely related to canine oral papillomavirus (COPV). A 384 bp non-coding region (NCR) was found between the end of L1 and the beginning of E6, and a 1·3 kbp NCR was located between the end of E2 and the beginning of L2. Phylogenetic analysis placed FdPV in the E3 clade with COPV. Both viruses contain the atypical second NCR, which has no homology with sequences in existing databases.

Polyomavirus mutants E, Q and H, expressing non-myristylated VP2, were generated by replacing the N-terminal glycine residue with glutamic acid, glutamine or histidine, respectively. Viruses mutated in either VP2 or VP3 translation initiation codons were also prepared. All mutated genomes, when transfected into murine host cells, gave rise to viral particles. Infectivity of VP2− and VP3− viruses, as measured by the number of cells expressing viral antigens, was dramatically diminished, indicative of defects in the early stages of infection. In contrast, the absence of a myristyl moiety on VP2 did not substantially affect the early steps of virus infection. No differences in numbers of cells expressing early or late viral antigens were observed between wild-type (wt) and E or Q myr− viruses during the course of a life cycle. Furthermore, no delay in virus DNA replication was detected. However, when cells were left for longer in culture, the number of infected cells, measured by typical virus bursts, was much lower when mutant rather than wt genomes were used. In situ, cell fractionation studies revealed differences in the interaction of viral particles with host cell structures. The infectivity of mutants was affected not only by loss of the myristyl group on VP2, but also, and to a greater extent, by alterations of the N-terminal amino acid composition.

The incidence of testicular germ cell cancer, which is the most common cancer among young male adults, is increasing. The aetiology remains unknown, although a virus has been proposed. A previous study has shown a high prevalence of human parvovirus B19 (B19) DNA in the testes of patients with testicular germ cell tumours (85%) and suggested that B19 may play a role in tumour development. To address this question of causality, seroreactivity to B19 was studied among cases (n=80) and controls (n=241) using serum samples drawn before the onset of disease, in addition to an elucidation of the frequency of virus DNA in a retrospectively collected 2-year testicular carcinoma series. No association was found between B19 seropositivity and the risk of testicular cancer (odds ratio=1·03; 95% confidence interval=0·60–1·77) nor was there any dose-response relation (P for trend=0·53). This study did, however, confirm the observation that B19 DNA can be detected in testicular carcinoma tissue, as 4 of 24 cases were found to be positive, while no B19 DNA could be detected in the control cases. It is speculated that this finding may be due to susceptibility of the carcinoma cells to B19 virus owing to high-level expression of the viral receptor glycosphingolipid (Gb4) and possible other putative cellular factors resulting in a localized persistence initiated after the development of cancer.