HSV-2

Use of transcriptional profiling to delineate the initial response of mice to intravaginal herpes simplex virus type 2 infection.

Cherpes TL¹, Harvey SA, Phillips JM, Vicetti Miguel RD, Melan MA, Quispe Calla NE, Hendricks RL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA. cherpest@pitt.edu

 

Abstract

Intravaginal (ivag) infection of mice with herpes simplex virus type 2 (HSV-2) causes genital tissue damage, quickly followed by development of fatal encephalopathy. To delineate initial host responses generated by HSV-2 infection, here oligonucleotide microarrays compared gene expression in vaginal tissue from uninfected mice and mice 1, 2, 3, 4, 5, 6, or 7 days after ivag infection with 10(4) pfu HSV-2. While comparison of mRNA expression in uninfected and HSV-infected vaginal tissue detected few changes during the first 2 days post infection (dpi), there were 156 genes whose expression was first significantly altered 3 dpi that remained significantly modified at all later time points examined. These 156 genes were significantly enriched in canonical pathways associated with interferon (IFN) signaling, activation of IFN elements by intracellular pattern recognition receptors, and antiviral immunity induced by cytosolic RIG-like receptors. Evaluation of this gene set with the National Center for Biotechnology Information Gene and INTERFEROME databases corroborated pathway analysis, as function of most (53%) were linked to IFN-mediated host immunity. In the final set of experiments, ivag administration of the Toll-like receptor 3 agonist polyinosinic: polycytidylic acid (poly I:C) 24 h before ivag HSV-2 infection reduced the incidence of genital pathology and encephalopathy, while these poly I:C-treated mice were subsequently protected from ocular HSV-2 challenge lethal to uninfected controls. The latter results imply that the exuberant antiviral immunity produced in our experimental model is simply formed too late to prevent viral replication and dissemination, and that poly I:C-induced formation of an antiviral state protecting against primary ivag infection also permits development of HSV-specific protective immunity.

Viral Immunol. 2013 Jun;26(3):172-9. doi: 10.1089/vim.2012.0093. Epub 2013 May 2.

 http://online.liebertpub.com/doi/abs/10.1089/vim.2012.0093

Md. Rodolfo Vicetti. Ex-miembro del GII.

Cáncer y Citocinas

Chemokine-Derived Peptides: Novel Antimicrobial and Antineoplasic Agents.

 

Valdivia-Silva J1,2, Medina-Tamayo J1,2, Garcia-Zepeda EA3,4.

¹Chemokine Biology Research Laboratory, Programa Institucional de Investigación en Cancer de Mama, Mexico DF 04510, Mexico.
²Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico.
³Chemokine Biology Research Laboratory, Programa Institucional de Investigación en Cancer de Mama, Mexico DF 04510, Mexico. garciaze@unam.mx.
⁴Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico DF 04510, Mexico. garciaze@unam.mx.

 

Abstract

Chemokines are a burgeoning family of chemotactic cytokines displaying a broad array of functions such as regulation of homeostatic leukocyte traffic and development, as well as activating the innate immune system. Their role in controlling early and late inflammatory stages is now well recognized. An improper balance either in chemokine synthesis or chemokine receptor expression contributes to various pathological disorders making chemokines and their receptors a useful therapeutic target. Research in this area is progressing rapidly, and development of novel agents based on chemokine/ chemokine receptors antagonist functions are emerging as attractive alternative drugs. Some of these novel agents include generation of chemokine-derived peptides (CDP) with potential agonist and antagonist effects on inflammation, cancer and against bacterial infections. CDP have been generated mainly from N- and C-terminus chemokine sequences with subsequent modifications such as truncations or elongations. In this review, we present a glimpse of the different pharmacological actions reported for CDP and our current understanding regarding the potential use of CDP alone or as part of the novel therapies proposed in the treatment of microbial infections and cancer.

KEYWORDS:

cancer; chemokine; chemokine receptors; cytokines; inflammation; microbial infections; peptides

Int J Mol Sci. 2015 Jun 8;16(6):12958-12985.

http://www.mdpi.com/1422-0067/16/6/12958

Md PhD Julio Valdivia Silva. Fundador del GII