Articles of Significant Interest Selected from This Issue by the Editors

Human immunodeficiency virus type 1 (HIV-1) gp41 plays a critical role in the viral fusion process and serves as an important target for anti-HIV-1 drug development. Zhu et al. (p. 9359-9368) identified a novel gp41 core-binding molecule, designated P20, which is effective at blocking HIV-1 Env-mediated syncytium formation and inhibiting infection by a broad spectrum of HIV-1 strains with distinct subtypes and coreceptor tropism. Therefore, this peptide can be used for developing novel HIV fusion inhibitors and as a probe for studying the membrane fusogenic mechanism of HIV.

Hepatitis B virus (HBV) requires the HBX gene for productive infection, but its precise role remains elusive. Zhang et al. (p. 9326-9331) show that the proteasome complex is important for HBX function. A proteasome inhibitor markedly enhances the replication of HBV defective for HBX but has a minor effect on wild-type HBV replication in two in vivo models. This work suggests that HBX inhibits proteasome activities that may interfere with HBV replication, thus providing a potential target for anti-HBV therapeutics.

Varicella-zoster virus (VZV) modulates cytokine signaling pathways by regulating activation of cellular transcription factors. Sen et al. (p. 9240-9253) show that VZV can inhibit beta interferon (IFN-β) and ISG induction by inhibiting TBK1-mediated IRF3 activation via the IE62 protein. This work has led to the identification of a new function for IE62 in VZV infection. IE62 is suggested to be a viral “sink” that depletes both the kinase (TBK1) and substrate (IRF3) required for optimal IFN-β induction. The observations reported describe a novel mechanism of IFN-β inhibition among herpesviruses.

Memory CD4 T cells persist after influenza virus infection and vaccination in humans, although their protective potential remains undefined. Teijaro et al. (p. 9217-9226) demonstrate, using a mouse model, that influenza virus-specific memory CD4 T cells can direct enhanced viral clearance in the lungs and protection against lethal challenge in the absence of B cells or CD8 T cells through a gamma interferon-dependent mechanism. These results indicate that secondary responses by memory CD4 T cells are independent of helper functions, with important implications for designing cross-protective vaccines through targeting the generation of long-lived memory CD4 T cells.

Sulfolobus turreted icosahedral virus experiences an extracellular environment of near boiling acid. Khayat et al. (p. 9575-9583) describe treatments that (i) strip a single type of protein from the pentameric turrets, altering interactions of the major capsid protein (MCP) with an internal membrane; (ii) remove the turrets and much of the MCP, forming partially decorated, genome-containing, phosolipid spheres; or (iii) remove all protein from the phospholipid, leaving a putative entry intermediate prepared to fuse with cellular membranes for double-stranded DNA delivery. These studies offer insights into the properties of virus particles that ensure survival in harsh extracellular environments while favoring efficient and controlled intracellular virion disassembly.