Articles of Significant Interest Selected from This Issue by the Editors -- 84 (18): 8997 -- The Journal of Virology

Journal of Virology, September 2010, p. 8997, Vol. 84, No. 18
0022-538X/10/$012.00+0 doi:10.1128/JVI.01520-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.


SPOTLIGHT


Articles of Significant Interest Selected from This Issue by the Editors
A Novel Peptide Inhibiting Human Immunodeficiency Virus Type 1 Entry
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. [see this article and comments in spanish below]

The Proteasome as an In Vivo Target of Hepatitis B Virus HBX Protein

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 IE62 Protein Inhibits Beta Interferon Induction by Blocking IRF3 Function

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.

Mechanisms of Protection against Influenza Virus Infection by Memory CD4 T Cells

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.

Particle Stability of Virions Purified from Extreme Environments

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.




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Journal of Virology, September 2010, p. 8997, Vol. 84, No. 18
0022-538X/10/$012.00+0 doi:10.1128/JVI.01520-10
Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Articles of Significant Interest Selected from This Issue by the Editors -- 84 (18): 8997 -- The Journal of Virology





SIDA
Actualidad Ultimas noticias - JANOes y agencias -
Un nuevo fármaco experimental impide al VIH infectar a las células
JANO.es y agencias · 20 Agosto 2010 09:39

El medicamento se desarrolla en forma de microbicida vaginal y podría utilizarse frente a otros virus, según publica el “Journal of Virology”



Científicos de la Universidad de Utah (Estados Unidos) han logrado desarrollar en su laboratorio un prometedor fármaco, bautizado como PIE12-Trimer, que sería capaz de bloquear el virus del sida, impidiendo que ataque a las células de la persona infectada y se reproduzca en el organismo.

El hallazgo, publicado en el Journal of Virology, sólo se ha mostrado eficaz en modelos animales, aunque los investigadores esperan que las pruebas en humanos comiencen en 2 o 3 años y avanzan que será desarrollado como un microbicida vaginal de uso tópico, si los experimentos tienen éxito.

PIE12-Trimer está compuesto por tres péptidos-D combinados que bloquean una región de la superficie del virus del sida fundamental para que penetre en la célula. “Ahora los ensayos clínicos determinarán si PIE12-Trimer es tan eficaz en las personas como lo es en el laboratorio”, explica el autor principal del estudio, Michael Kay.

El nuevo fármaco ha sido diseñado como un único “condensador de resistencia” que provee a la célula de una defensa eficaz contra la aparición de virus resistentes a los fármacos actuales. Los péptidos tienen en general un gran potencial terapéutico, pero a menudo pierden eficacia por su rápida degradación una vez entran en el organismo.

En este sentido, los péptidos-D son versiones modificadas de los péptidos naturales que tienen una mayor resistencia y no se degradan tan fácilmente en el cuerpo, lo que les otorga una mayor potencia y eficacia a largo plazo frente al sida. A pesar de estas ventajas, ningún péptidos-D ha sido aún completado para su uso en humanos.

“El VIH puede desarrollar rápidamente resistencias frente a los actuales medicamentos, por ello es necesario la investigación y el desarrollo constante de nuevos fármacos con la esperanza de ir un paso por delante de la evolución del virus”, comenta Kay.

De hecho, en su dispersión global, el VIH se presenta en múltiples versiones y tiene la capacidad de transformarse rápidamente para ofrecer resistencias a los fármacos utilizados habitualmente.

Journal of Virology 2010:84:8997
Articles of Significant Interest Selected from This Issue by the Editors -- 84 (18): 8997 -- The Journal of Virology

Journal of Virology
http://jvi.asm.org/

University of Utah
http://www.utah.edu/portal/site/uuhome/

Actualidad Ultimas noticias - JANOes y agencias - Un nuevo farmaco experimental impide al VIH infectar a las celulas - JANO.es - ELSEVIER