Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (

Background: Viral suppressors of RHIM-dependent activation of pro-necrotic RIP3 kinase are crucial for successful infection in mice. Results: Human CMV blocks TNF-induced and murine CMV-induced necroptosis after RIP3 activation. Conclusion: Necrotic membrane leakage is blocked in infected cells despite the activation of MLKL. Significance: Viral inhibition of necroptosis will facilitate understanding of the final steps in this pathway.

Objective: We have reexamined hepatitis B virus subtypes to determine the role of specific HBsAg amino acids in serologic reactivity because of problematic genotype/subtype associations seen in a set of geographically diverse serum specimens. Methods: We obtained DNA sequences for 491 HBsAg-positive specimens from geographically distinct locations, determined their genotypes through phylogenetic analysis, and subtyped the specimens using an algorithm derived from published data on the molecular basis of HBsAg subtype reactivity. Problematic samples were subtyped serologically to resolve conflicts based on the amino acid sequence alone. Results: Three isolates were found to have unusual genotype/subtype associations. Examination of the isolates’ amino acid sequences suggested amino acid positions 122, 127, 140, 159 and 160 can be used to determine subtype reactivity from HBsAg amino acid sequences, while position 134, previously thought to play a role, is no longer important. Conclusions: This re-examination of hepatitis B virus subtypes shows the involvement of amino acid positions 122, 127, 140, 159 and 160 in HBsAg reactivity. While d, y, and r reactivities are controlled by single amino acid changes, w reactivity is determined by positions 122, 127, 140, and 159.

To examine the range of selective processes that potentially operate when poorly binding influenza viruses adapt to replicate more efficiently in alternative environments, we passaged a virus containing an attenuating mutation in the hemagglutinin (HA) receptor binding site in mice and characterized the resulting mutants with respect to the structural locations of mutations selected, the replication phenotypes of the viruses, and their binding properties on glycan microarrays. The initial attenuated virus had a tyrosine-to-phenylalanine mutation at HA1 position 98 (Y98F), located in the receptor binding pocket, but viruses that were selected contained second-site pseudoreversion mutations in various structural locations that revealed a range of molecular mechanisms for modulating receptor binding that go beyond the scope that is generally mapped using receptor specificity mutants. A comparison of virus titers in the mouse respiratory tract versus MDCK cells in culture showed that the mutants displayed distinctive replication properties depending on the system, but all were less attenuated in mice than the Y98F virus. An analysis of receptor binding properties confirmed that the initial Y98F virus bound poorly to several different species of erythrocytes, while all mutants reacquired various degrees of hemagglutination activity. Interestingly, both the Y98F virus and pseudoreversion mutants were shown to bind very inefficiently to standard glycan microarrays containing an abundance of binding substrates for most influenza viruses that have been characterized to date, provided by the Consortium for Functional Glycomics. The viruses were also examined on a recently developed microarray containing glycans terminating in sialic acid derivatives, and limited binding to a potentially interesting subset of glycans was revealed. The results are discussed with respect to mechanisms for HA-mediated receptor binding, as well as regarding the species of molecules that may act as receptors for influenza virus on host cell surfaces.

Epidemiological evidence suggests that childhood acute lymphoblastic leukaemia (ALL) may be initiated by an in infection in utero. Adenovirus DNA was detected in 13 of 49 neonatal blood spots from ALL patients but only in 3 of 47 controls (P ¼ 0.012) suggesting a correlation between prenatal adenovirus infection and the development of ALL