Table of Contents

Abstract: Cell-to-cell spread of HIV-1 between CD4⁺ T cells takes place at multimolecular structures called virological synapses. A defining feature of the virological synapse is polarization of viral assembly and budding at sites of T cell-T cell contact. Recent work is beginning to address how viral proteins are targeted to the virological synapse and the molecular mechanisms that regulate HIV-1 egress by cell-to-cell spread. This review discusses our current understanding of these processes and considers how T cell polarization during other forms of intercellular communication may provide insight into HIV-1 assembly and dissemination.

Abstract: While 25 compounds have been formally licensed for the treatment of HIV infection (AIDS), only seven licensed products are currently available for the treatment of chronic hepatitis B virus (HBV) infection: interferon-α, pegylated interferon-α, lamivudine, adefovir (dipivoxil), entecavir, telbivudine and tenofovir (disoproxil fumarate). In contrast to the treatment of HIV infections where the individual drugs are routinely used in combination, for the treatment of chronic HBV infection the individual drugs are generally used in monotherapy. In principle, combination drug therapy should allow reducing the likelihood of drug-resistant development.

Abstract: Viruses from several families use direct cell-to-cell infection to disseminate between cells. Retroviruses are a relatively recent addition to this list, and appear to spread cell-to-cell by induction of multimolecular complexes termed virological synapses that assemble at the interface between infected and receptor-expressing target cells. Over the past five years, detailed insight into the cellular and molecular basis of virological synapse-mediated retroviral cell-to-cell spread has been obtained, but important questions and controversies have been raised that remain to be resolved. This review will focus on recent advances in the field with emphasis on areas in which work still needs to be done.

Abstract: The poxvirus vaccinia virus (VV) served as the model virus for which the first antivirals, the thiosemicarbazones, were identified. This dates back to 1950; and, although there is at present no single antiviral drug specifically licensed for the chemotherapy or -prophylaxis of poxvirus infections, numerous candidate compounds have been described over the past 50 years. These compounds include interferon and inducers thereof (i.e., polyacrylic acid), 5-substituted 2’-deoxyuridines (i.e., idoxuridine), IMP dehydrogenase inhibitors, S-adenosylhomocysteine hydrolase inhibitors, acyclic nucleoside phosphonates (such as cidofovir) and alkoxyalkyl prodrugs thereof (such as CMX001), viral egress inhibitors (such as tecovirimat), and cellular kinase inhibitors (such as imatinib).

Abstract: A recently solved structure of the aquareovirus virion (Zhang, X; Jin, L.; Fang, Q; Hui, W.H.; Zhou Z.H. 3.3 Å Cryo-EM Structure of a Nonenveloped Virus Reveals a Priming Mechanism for Cell Entry. Cell 2010, 141, 472-482 [1]) provides new insights into the order of entry events, as well as confirming and refining several aspects of the entry mechanism, for aquareovirus and the related orthoreovirus. In particular, the structure provides evidence of a defined order for the progressive proteolytic cleavages of myristoylated penetration protein VP5 that prime the virion for membrane penetration. These observations reinforce the concept that, much like enveloped viruses, nonenveloped virions often undergo priming events that lead to a meta-stable state, preparing the virus for membrane penetration under the appropriate circumstances. In addition, this and other recent studies highlight the increasing power of electron cryomicroscopy to analyze large, geometrically regular structures, such as icosahedral viruses, at atomic resolution.