Virus Entry
The latest issue of the Journal of Viral Entry (free online) has some interesting articles:
CCR5 Antagonists in the Clinic: A Review. J Viral Entry 2008 3: 42–53. New antiretroviral agents, in both existing and new classes, have expanded the range of therapeutic options for treatment-experienced patients infected with HIV, and shifted the therapeutic goals for patients with previously limited drug options. CCR5 antagonists have demonstrated clear benefits over placebo in highly treatment-experienced subjects, with favorable toxicity and safety profiles in both treatment-experienced and naïve individuals. Virus tropism testing is crucial in determining susceptibility to CCR5 antagonists and refinement of current assays may better define those for whom these agents are suitable. Pending pharmacokinetic and longitudinal tropism studies, CCR5 antagonists may provide an ideal alternative for patients who have toxicity or tolerability issues with other antiretrovirals. This article reviews the role of CCR5 inhibitors in clinical practice.
Chemokine Receptors CCR5 and CXCR4: More Than Mere Portals for HIV Type 1 Entry. J Viral Entry 2008 3:54–60. Chemokines and their specific G protein-coupled receptors orchestrate the migration of leukocytes under both homeostatic and inflammatory conditions, which constitutes a pivotal part of the host immune defense. This has not gone unnoticed by microbes, which utilize both chemokines and their receptors to subvert the immune system for their own benefit. Perhaps the best known example of such exploitation is the use of chemokine receptors CCR5 and CXCR4 by HIV type 1 to gain entry into macrophages and T cells, respectively. This has helped fuel intensive research into both molecules, leading to a greater understanding of the fascinating biology of these receptors. This review discusses the properties and roles of CCR5 and CXCR4 in health and disease, and highlights current strategies for targeting both receptors as potential therapies in a variety of diseases.
Mechanism and Inhibition of Hepatitis C Virus Entry. J Viral Entry 2008 3: 61–67. Inhibition of viruses at the stage of viral entry provides a means for therapeutic intervention. Owing to difficulties in propagating hepatitis C virus (HCV) in cell culture, the study of molecules that block HCV entry into host cells has long been hampered. However, the development of surrogate models and the recent progress in amplification of HCV in vitro have finally allowed the study of HCV entry, as well as the identification and characterization of inhibitors targeting the early steps of the virus life cycle. Recent data indicate that HCV enters target cells in a complex multistep process that involves several entry factors, each stage providing an opportunity to be exploited for design of new anti- HCV drugs. Today, polyclonal and monoclonal neutralizing antibodies constitute the most promising entry inhibitors, and the therapeutic activities of some of these are currently being evaluated in clinical trials. Furthermore, other types of molecules that specifically inhibit HCV entry have recently been reported. This review discusses recent advances in the understanding of the mechanisms of HCV cell entry, and the potential antiviral activity of some inhibitors of this major stage in the HCV lifecycle.
Tags: Biology, HIV/AIDS, Medicine, Microbiology, Science, Virology
