After hepatitis B virus (HBV) infectionThe incubation period of a viral disease refers to the time between infection and the onset of symptoms, and has been believed to represent the phase of active viral replication before an effective host immune response. This period is generally long after infection with noncytopathic viruses such as hepatitis B virus (HBV), 1 in contrast to other viral diseases. [2][3][4] The development of symptoms, which may occur up to 6 months after HBV infection, 5 has been assumed to mark the onset of viral control by the immune system. 1 However, the observation of marked reductions in virus levels before liver injury in the chimpanzee model of HBV infection, 6 and of cytotoxic T lymphocyte (CTL)-mediated viral clearance in the absence of cytolysis, in a transgenic mouse model of HBV infection, 7 has challenged the evidence that HBV control is predominantly caused by CTL-mediated tissue injury. It is, therefore, possible that immunologic events important for the control of HBV may already be present during the long incubation phase of primary infection. However, patients are usually only diagnosed after the development of symptoms: thus, it has been difficult to study the relationship between viral dynamics and liver injury, and whether the incubation phase of HBV infection in humans represents a period of ongoing viral replication in the presence of a deficient immune response. 8 During a single-source outbreak of HBV infection, in which 30 patients were infected through a skin-piercing procedure known as autohemotherapy, 9 a number of patients were identified before the onset of clinical hepatitis. The recent development of immunologic techniques to directly quantify virusspecific lymphocytes, 10,11 enabling the dynamics of CD8 and CD4 responses during viral infections to be investigated, provided a unique opportunity to study the interaction among virus, clinical disease, and host immune responses from the incubation phase of acute HBV infection. PATIENTS AND METHODS Patients.Five patients (all women, mean age 54 years, range 37-71) were identified during the incubation phase of acute hepatitis B, and were longitudinally followed up through the course of the disease. Their infection was diagnosed on the basis of finding a positive serum hepatitis B surface antigen (HBsAg), HBV DNA by polymerase chain reaction, normal or minimally raised serum alanine transaminase (ALT) levels, a marker of hepatocyte damage, 12 and no symptoms of clinical acute hepatitis. Each patient was infected with the same variant of HBV, as assessed by viral genome sequencing and

The identified co-circulating HCV lineages belong to different subtypes and genotypes, implying that rather than viral change, the epidemic is due to permucosal transmission factors that should be the focus of public health interventions.

The cytotoxic T-cell response in chronic hepatitis B virus (HBV) infection has been described as weak and mono-or oligospecific in comparison to the more robust virus-specific T-cell response present in resolved infection. However, chronic hepatitis B is a heterogeneous disease with markedly variable levels of virus replication and liver disease activity. Here we analyzed (both directly ex vivo and after in vitro stimulation) the HBV-specific CD8 T-cell responses against structural and nonstructural HBV proteins longitudinally in patients with different patterns of chronic infections. We found that the profiles of virus-specific CD8؉ -T-cell responses during chronic infections are highly heterogeneous and influenced more by the level of HBV replication than by the activity of liver disease. An HBV DNA load of <10 7 copies/ml appears to be the threshold below which circulating multispecific HBV-specific CD8 ؉ T cells are consistently detected. Furthermore, CD8؉ T cells with different specificities are differentially regulated during chronic infections. HBV core-specific CD8 ؉ T cells are associated with viral control, while CD8 ؉ T cells specific for envelope and polymerase epitopes can occasionally be found in the setting of high levels (>10 7 copies) of HBV replication. These findings have implications for the design of immunotherapy for chronic HBV infections.

The movement of magma through the shallow crust and the impact of subsurface sill complexes on the hydrocarbon systems of prospective sedimentary basins has long been an area of interest and debate. Based on 3D seismic reflection and well data, we present a regional analysis of the emplacement and magmatic plumbing system of the Palaeogene Faroe-Shetland Sill Complex (FSSC), which is intruded into the Mesozoic and Cenozoic sequences of the Faroe-Shetland Basin (FSB). Identification of magma flow directions through detailed seismic interpretation of approximately 100 sills indicates that the main magma input zones into the FSB were controlled primarily by the NE-SW basin structure that compartmentalise the FSB into its constituent sub-basins. An analysis of well data shows that potentially up to 88% of sills in the FSSC are <40 m in thickness, and thus below the vertical resolution limit of seismic data at depths at which most sills occur. This resolution limitation suggests that caution needs to be exercised when interpreting magmatic systems from seismic data alone, as a large amount of intrusive material could potentially be missed. The interaction of the FSSC with the petroleum systems of the FSB is not well understood. Given the close association between the FSSC and potential petroleum migration routes into some of the oil/gas fields (e.g. Tormore), the role the intrusions may have played in compartmentalisation of basin fill needs to be taken fully into account to further unlock the future petroleum potential of the FSB.

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