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Influenza A virus forms enveloped particles that can vary in shape between pleiomorphic spheres and filaments of up to 30 μm in length. Bruce et al (p. 5848-5859) show that Rab11 and Rab11 family-interacting protein 3 (FIP3) are involved in the formation of filamentous virions. Rab11, perhaps in association with other proteins, is essential for the final scission stage to release spherical virus particles. These data highlight an important new cellular pathway involved in virus budding.
Nonstructural protein NS1 of the oncolytic rat parvovirus H-1PV is a major cytotoxic effector. However, the means by which NS1 kills cells are largely unknown. Hristov et al. (p. 5909-5922) demonstrate that NS1 induces DNA damage, accumulation of cells in the G2 stage of the cell cycle, and apoptotic cell death. Remarkably, NS1 triggers increased levels of intracellular reactive oxygen species as a precursor to the cytostatic and cytotoxic effects of H-1PV infection. These findings shed light on mechanisms of cytotoxicity mediated by H-1PV NS1.
An effective prophylactic vaccine remains the best hope to curb the human immunodeficiency virus (HIV) pandemic. Although great strides have been made toward understanding immune responses to HIV during chronic infection, correlates of immune protection are poorly understood. Barnett et al. (p. 5975-5985) used an alphavirus vector prime followed by an envelope glycoprotein boost vaccine approach to show that the presence of virus neutralizing and high avidity antibodies correlate with protection against infection in a relevant animal model. This work provides a pathway for future development of an effective HIV vaccine.
Attenuated viral vaccines have the potential to revert to virulence and can be contaminated with adventitious viruses. Victoria et al. (p. 6033-6040) used deep sequencing and panmicrobial arrays to probe for non-vaccine viral nucleic acids in eight human viral vaccines. Minority reversion mutations were not detected after deep sampling of the three poliovirus serotypes in the oral vaccine quasispecies. Endogenous retroviral nucleic acids from the producer cell lines and DNA from a contaminating porcine circovirus 1, none thought capable of infecting vaccinees, were detected. Metagenomics and microarrays can help maintain the safety of attenuated viral vaccines and other biologically derived products.
Alterations in the host proteome during severe acute respiratory syndrome coronavirus (SARS-CoV) replication have not been precisely defined. Zhang et al. (p. 6050-6059) provide an overview of changes in host cell protein expression following SARS-CoV infection by using quantitative proteomics. Functional studies revealed that one of the identified host proteins, BAG3, is required for SARS-CoV replication. This work enhances an understanding of SARS-CoV replication and provides a potential target for antiviral therapy.