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Immune evasion

Eun-Kyung Kwon, Chan-Ki Min, Yuri Kim, Jae-Won Lee, Abdimadiyeva Aigerim, Sebastian Schmidt, Hyun-Jun Nam, Seong Kyu Han, Kuglae Kim, Jeong Seok Cha, Hoyoung Kim, Sanguk Kim, Hyun-Soo Cho, Myung-Sik Choi, Nam-Hyuk Cho
Members of the herpesviral family use multiple strategies to hijack infected host cells and exploit cellular signaling for their pathogenesis and latent infection. Among the most intriguing weapons in the arsenal of pathogenic herpesviruses are the constitutively active virally-encoded G protein-coupled receptors (vGPCRs). Even though vGPCRs contribute to viral pathogenesis such as immune evasion and proliferative disorders, the molecular details of how vGPCRs continuously activate cellular signaling are largely unknown...
October 14, 2016: Biochimica et Biophysica Acta
Christian Spoerry, Pontus Hessle, Melanie J Lewis, Lois Paton, Jenny M Woof, Ulrich von Pawel-Rammingen
Recently we have discovered an IgG degrading enzyme of the endemic pig pathogen S. suis designated IgdE that is highly specific for porcine IgG. This protease is the founding member of a novel cysteine protease family assigned C113 in the MEROPS peptidase database. Bioinformatical analyses revealed putative members of the IgdE protease family in eight other Streptococcus species. The genes of the putative IgdE family proteases of S. agalactiae, S. porcinus, S. pseudoporcinus and S. equi subsp. zooepidemicus were cloned for production of recombinant protein into expression vectors...
2016: PloS One
Miguel Pinto, Vítor Borges, Minia Antelo, Miguel Pinheiro, Alexandra Nunes, Jacinta Azevedo, Maria José Borrego, Joana Mendonça, Dina Carpinteiro, Luís Vieira, João Paulo Gomes
Insights into the genomic adaptive traits of Treponema pallidum, the causative bacterium of syphilis, have long been hampered due to the absence of in vitro culture models and the constraints associated with its propagation in rabbits. Here, we have bypassed the culture bottleneck by means of a targeted strategy never applied to uncultivable bacterial human pathogens to directly capture whole-genome T. pallidum data in the context of human infection. This strategy has unveiled a scenario of discreet T. pallidum interstrain single-nucleotide-polymorphism-based microevolution, contrasting with a rampant within-patient genetic heterogeneity mainly targeting multiple phase-variable loci and a major antigen-coding gene (tprK)...
October 17, 2016: Nature Microbiology
Yu Chen, Xiaoling Deng, Junfang Deng, Jiehua Zhou, Yuping Ren, Shengxuan Liu, Deborah J Prusak, Thomas G Wood, Xiaoyong Bao
Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion...
October 13, 2016: Virology
Salvador Iborra, María Martínez-López, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, Helena M Izquierdo, Clare L Abram, Daiki Mori, Yolanda Campos-Martín, Rosa María Reguera, Benjamin Kemp, Sho Yamasaki, Matthew J Robinson, Manuel Soto, Clifford A Lowell, David Sancho
C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs)...
October 5, 2016: Immunity
Jia-Yun C Tsai, Jacelyn M S Loh, Fiona Clow, Natalie Lorenz, Thomas Proft
Group A Streptococcus (GAS), or Streptococcus pyogenes, is a human pathogen that causes diseases ranging from skin and soft tissue infections to severe invasive diseases, such as toxic shock syndrome. Each GAS strain carries a particular pilus type encoded in the variable fibronectin-binding, collagen-binding, T antigen (FCT) genomic region. Here we describe the functional analysis of the serotype M2 pilus encoded in the FCT-6 region. We found that, in contrast to other investigated GAS pili, the ancillary pilin 1 lacks adhesive properties...
October 14, 2016: Molecular Microbiology
Tsai-Wen Wan, Olga E Khokhlova, Yasuhisa Iwao, Wataru Higuchi, Wei-Chun Hung, Ivan V Reva, Olga A Singur, Vladimir V Gostev, Sergey V Sidorenko, Olga V Peryanova, Alla B Salmina, Galina V Reva, Lee-Jene Teng, Tatsuo Yamamoto
ST8/SCCmecIV community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been a common threat, with large USA300 epidemics in the United States. The global geographical structure of ST8/SCCmecIV has not yet been fully elucidated. We herein determined the complete circular genome sequence of ST8/SCCmecIVc strain OC8 from Siberian Russia. We found that 36.0% of the genome was inverted relative to USA300. Two IS256, oppositely oriented, at IS256-enriched hot spots were implicated with the one-megabase genomic inversion (MbIN) and vSaβ split...
2016: PloS One
Gu-Choul Shin, Hong Seok Kang, Ah Ram Lee, Kyun-Hwan Kim
Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells...
October 14, 2016: Autophagy
Meghan Zuck, Tisha Ellis, Anthony Venida, Kevin Hybiske
The precise strategies that intracellular pathogens use to exit host cells have a direct impact on their ability to disseminate within a host, transmit to new hosts, and engage or avoid immune responses. The obligate intracellular bacterium Chlamydia trachomatis exits the host cell by two distinct exit strategies, lysis and extrusion. The defining characteristics of extrusions, and advantages gained by Chlamydia within this unique double-membrane structure are not well understood. Here, we define extrusions as being largely devoid of host organelles, comprised mostly of Chlamydia elementary bodies, and containing phosphatidylserine on the outer surface of the extrusion membrane...
October 14, 2016: Cellular Microbiology
William J Liu, Shuguang Tan, Min Zhao, Chuansong Quan, Yuhai Bi, Ying Wu, Shuijun Zhang, Haifeng Zhang, Haixia Xiao, Jianxun Qi, Jinghua Yan, Wenjun Liu, Hongjie Yu, Yuelong Shu, Guizhen Wu, George F Gao
BACKGROUND:  The emergence of infections by the novel avian influenza A (H7N9) virus has posed a threat to human health. Cross-immunity between H7N9 and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated. METHODS:  We investigated the cellular and humoral immune responses against H7N9 and the 2009 pandemic H1N1 influenza viruses, by serological and T-cell-specific assays in a healthy population. The molecular bases of the cellular and humoral antigenic variability of H7N9 were illuminated by structural determination...
October 12, 2016: Journal of Infectious Diseases
Ruoxu Dou, Reiko Nishihara, Yin Cao, Tsuyoshi Hamada, Kosuke Mima, Atsuhiro Masuda, Yohei Masugi, Yan Shi, Mancang Gu, Wanwan Li, Annacarolina da Silva, Katsuhiko Nosho, Xuehong Zhang, Jeffrey A Meyerhardt, Edward L Giovannucci, Andrew T Chan, Charles S Fuchs, Zhi Rong Qian, Shuji Ogino
Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis...
October 13, 2016: Cancer Immunology Research
Yanping Fan, Xiaolin Wang, Ling Li, Zhenjiang Yao, Sidong Chen, Xiaohua Ye
While some studies have defined Staphylococcus aureus based on its clonal complex and resistance pattern, few have explored the relations between the genetic lineages and antibiotic resistance patterns and immune evasion cluster (IEC) genes. Our aim was to investigate the potential relationship between phenotypic and molecular characteristics so as to reveal livestock-associated S. aureus in humans. The study participants were interviewed, and they provided two nasal swabs for S. aureus analysis. All S. aureus and methicillin-resistant S...
2016: Frontiers in Microbiology
Peter Kraiczy
Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully survive in diverse host environments for a prolonged period of time. In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement...
2016: Frontiers in Immunology
Justin D Radolf, Ranjit K Deka, Arvind Anand, David Šmajs, Michael V Norgard, X Frank Yang
The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation 'the stealth pathogen'. Despite the many hurdles to studying syphilis pathogenesis, most notably the inability to culture and to genetically manipulate T. pallidum, in recent years, considerable progress has been made in elucidating the structural, physiological, and regulatory facets of T...
October 10, 2016: Nature Reviews. Microbiology
J Bethke, R Avendaño-Herrera
Streptococcus phocae is a beta-hemolytic, Gram-positive bacterium that was first isolated in Norway from clinical specimens of harbor seal (Phoca vitulina) affected by pneumonia or respiratory infection, and in 2005, this bacterium was identified from disease outbreaks at an Atlantic salmon farm. A recent comparative polyphasic study reclassified Streptococcus phocae as subsp. phocae and subsp. salmonis, and there are currently two S. phocae NCBI sequencing projects for the type strains ATCC 51973(T) and C-4(T)...
October 5, 2016: Marine Genomics
David C Chang, Long T Hoang, Ahmad Nazri Mohamed Naim, Hongping Dong, Mark J Schreiber, Martin L Hibberd, Min Jie Alvin Tan, Pei-Yong Shi
Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection...
October 4, 2016: Virology
Punsiri M Colonne, Caylin G Winchell, Daniel E Voth
Intracellular bacterial pathogens replicate within eukaryotic cells and display unique adaptations that support key infection events including invasion, replication, immune evasion, and dissemination. From invasion to dissemination, all stages of the intracellular bacterial life cycle share the same three-dimensional cytosolic space containing the host cytoskeleton. For successful infection and replication, many pathogens hijack the cytoskeleton using effector proteins introduced into the host cytosol by specialized secretion systems...
2016: Frontiers in Cellular and Infection Microbiology
Fernanda Tomiotto-Pellissier, Allan Henrique Depieri Cataneo, Tatiane Marcuso Orsini, Ana Paula Fortes Dos Santos Thomazelli, Gabriela Alcântara Dalevedo, Admilton Gonçalves de Oliveira, Luciano Aparecido Panagio, Idessania Nazareth Costa, Ivete Conchon-Costa, Wander Rogério Pavanelli, Ricardo Sergio Almeida
Galleria mellonella is an excellent invertebrate model for the study of diseases that involve interactions with cells from the innate immune system, since they have an innate immune system capable of recognizing the pathogens. Here we present for the first time, an alternative model for an in vitro phagocytic assay using hemocytes of G. mellonella larvae to study infection by Leishmania (Viannia) braziliensis. We showed that the insect phagocytic cells were able to engulf promastigotes. Furthermore, this infective form differentiated into the amastigote form inside those cells...
October 3, 2016: Journal of Microbiological Methods
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Francisco José Vázquez, Jorge Albareda, Marta Prades, Jaime Gosálvez, Rosa Roy, Pilar Zaragoza, Inmaculada Martín-Burriel, Clementina Rodellar
Mesenchymal stem cells (MSCs) have a great potential for treating equine musculoskeletal injuries. Although their mechanisms of action are not completely known, their immunomodulatory properties appear to be key in their functions. The expression of immunoregulatory molecules by MSCs is regulated by pro-inflammatory cytokines, so inflammatory priming of MSCs might improve their therapeutic potential. However, inflammatory environment could also increase MSC immunogenicity and decrease MSC viability and differentiation capacity...
October 6, 2016: Stem Cells and Development
Zixiang Zhu, Guoqing Wang, Fan Yang, Weijun Cao, Ruoqing Mao, Xiaoli Du, Xiangle Zhang, Chuntian Li, Dan Li, Keshan Zhang, Hongbing Shu, Xiangtao Liu, Haixue Zheng
: The role of retinoic acid-inducible gene I (RIG-I) in foot-and-mouth disease virus (FMDV)-infected cells remains unknown. Herein, we showed that RIG-I inhibits FMDV replication in host cells. FMDV infection increased the transcription of RIG-I, while it decreased RIG-I protein expression. A detailed analysis revealed that FMDV leader proteinase (L(pro)), as well as 3C proteinase (3C(pro)) and 2B protein, decreased RIG-I protein expression. L(pro) and 3C(pro) are viral proteinases that can cleave various host proteins and are responsible for several of the viral polyprotein cleavages...
October 5, 2016: Journal of Virology
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