Donatienne Blond | PubMed Health

PubMed2005

Hepatitis B small surface antigen particles are octahedral.

The infectious component of hepatitis B (HB) virus (HBV), the Dane particle, has a diameter of approximately 44 nm and consists of a double-layered capsid particle enclosing a circular, incomplete double-stranded DNA genome. The outer capsid layer is formed from the HB surface antigen (HBsAg) and lipid, whereas the inner layer is formed from the HB core Ag assembled into an icosahedral structure. During chronic infection HBsAg is expressed in large excess as noninfectious quasispherical particles and tubules with approximately 22-nm diameter. Here, we report cryo-EM reconstructions of spherical HBsAg particles at approximately 12-A resolution. We show that the particles possess different diameters and have separated them into two predominant populations, both of which have octahedral symmetry. Despite their differing diameters, the two forms of the particle have the same mass and are built through conformational switching of the same building block, a dimer of HBsAg. We propose that this conformational switching, combined with interactions with the underlying core, leads to the formation of HBV Dane particles of different sizes, dictated by the symmetry of the icosahedral core.

Animals↗

PubMed2002

Differential induction of interleukin-1beta and tumour necrosis factor-alpha may account for specific patterns of leukocyte recruitment in the brain.

In peripheral tissue, IL-1beta has been shown to induce TNFalpha expression and vice versa, resulting in mixed neutrophil and mononuclear cell recruitment to the site of injury. This has led to the concept of crosstalk in peripheral cytokine signalling pathways. In the brain parenchyma, however, restricted patterns of leukocyte recruitment following the focal injection of pro-inflammatory agents into the brain are observed. This study investigates the expression of the principal pro-inflammatory cytokines--IL-1beta and TNFalpha--in the brain after IL-1beta, TNFalpha, NMDA or endotoxin injection into the brain parenchyma of rats. Each of these agents gives rise to a distinct pattern of acute leukocyte recruitment at 24 h. We found that IL-1beta induces de novo synthesis of additional IL-1beta but not TNFalpha, as determined by RT-PCR and ELISA, and TNFalpha does not induce either itself or IL-1beta. Injection of NMDA results in IL-1beta, but not TNFalpha up-regulation. Injection of IL-1beta or NMDA is associated with neutrophil recruitment whereas injection of TNFalpha is associated with mononuclear cell recruitment. Following injection of endotoxin, both TNFalpha and IL-1beta levels are elevated and neutrophils and mononuclear cells are recruited to the brain. These data suggest that the signalling pathways that are present in the periphery are modified in the brain and that differential induction of TNFalpha and IL-1beta may have a role in the atypical pattern of leukocyte recruitment observed in the brain.

Animals↗