抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The discovery of Toll-like receptors (TLRs) as components that recognize conserved structures in pathogens has greatly advanced understanding of how the body senses pathogen invasion, triggers innate immune responses and primes antigen-specific adaptive immunity. Although TLRs are critical for host defense, it has become apparent that loss of negative regulation of TLR signaling, as well as recognition of self molecules by TLRs, are strongly associated with the pathogenesis of inflammatory and autoimmune diseases. Furthermore, it is now clear that the interaction between TLRs and recently identified cytosolic innate immune sensors is crucial for mounting effective immune responses. Here we describe the recent advances that have been made by research into the role of TLR biology in host defense and disease.

/pdf/the-role-of-pattern-recognition-receptors-in-innate-immunity-39y77tlxza.pdf

The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors

Pattern Recognition Receptors and Inflammation

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Disclosed herein is a pharmacophore model for inhibiting anthrax lethal factor protease activity which comprises a first aromatic center A, a second aromatic center B, a first polar center C, a second polar center D, a third polar center E, and a neutral linker F. Also disclosed are small molecules fitting the pharmacophore model and compositions and methods of using thereof.

Inhibition of anthrax lethal factor protease

Authors: Andrew D. Haddow*, Aysegul Nalca, Franco D. Rossi, Lynn J. Miller, Michael R. Wiley, Unai Perez-Sautu, Samuel C. Washington, Sarah L. Norris, Suzanne E. WollenRoberts, Joshua D. Shamblin, Adrienne E. Kimmel, Holly A. Bloomfield, Stephanie M. Valdez, Thomas R. Sprague, Lucia M. Principe, Stephanie A. Bellanca, Stephanie S. Cinkovich, Luis Lugo-Roman, Lisa H. Cazares, William D. Pratt, Gustavo F. Palacios, Sina Bavari, Margaret L. Pitt, and Farooq Nasar

High Infection Rates in Adult Macaques Following Intravaginal or Intrarectal Zika Virus Inoculation

La presente invention concerne d'une maniere generale des compositions comportant des agents de potentialisation immuns a petite molecule (SMIP) de type benzonapthyridine qui sont capables de stimuler ou de moduler une reponse immunitaire chez un sujet qui a eu une pre ou post-exposition a un pathogene tel que le virus de la fievre hemorragique. L'invention concerne egalement des procedes de preparation et d'utilisation des compositions de SMIP de l'invention.

Compositions de benzonapthyridine et leurs utilisations

Several arenaviruses cause hemorrhagic fever (HF) diseases that are associated with high morbidity and mortality in humans. Accordingly, HF arenaviruses have been listed as top-priority emerging diseases for which countermeasures are urgently needed. Because arenavirus nucleoprotein (NP) plays critical roles in both virus multiplication and immune-evasion, we used an unbiased proteomic approach to identify NP-interacting proteins in human cells. DDX3, a DEAD-box ATP-dependent-RNA-helicase, interacted with NP in both NP-transfected and virus-infected cells. Importantly, DDX3 deficiency compromised the propagation of both Old and New World arenaviruses, including the HF arenaviruses Lassa and Junin viruses. The DDX3 role in promoting arenavirus multiplication correlated with both a previously un-recognized DDX3 contribution to type I interferon suppression in arenavirus infected cells and a positive effect of DDX3 on viral RNA synthesis. Our results uncover novel mechanisms used by arenavirus to exploit the host machinery and subvert immunity, singling out DDX3 as a potential host target for developing new therapies against highly pathogenic arenaviruses.

https://www.biorxiv.org/content/biorxiv/early/2017/11/25/224725.full.pdf

Sina Bavari

Papers

Inhibition of anthrax lethal factor protease

High Infection Rates in Adult Macaques Following Intravaginal or Intrarectal Zika Virus Inoculation

Compositions de benzonapthyridine et leurs utilisations

DDX3 is exploited by Arenaviruses to suppress type I interferons and favor their replication

Vaccins à superantigènes bactériens