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https://www.readbyqxmd.com/read/29045731/the-chimpanzee-model-of-viral-hepatitis-advances-in-understanding-the-immune-response-and-treatment-of-viral-hepatitis
#1
Robert E Lanford, Christopher M Walker, Stanley M Lemon
Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical research due to their close genetic relationship to humans and in many instances due to the lack of any other animal model. This review focuses on the contributions of the chimpanzee model to research on hepatitis viruses where chimpanzees represented the only animal model (hepatitis B and C) or the most appropriate animal model (hepatitis A). Research with chimpanzees led to the development of vaccines for HAV and HBV that are used worldwide to protect hundreds of millions from these diseases and, where fully implemented, have provided immunity for entire generations...
October 17, 2017: ILAR Journal
https://www.readbyqxmd.com/read/29045464/tip60-represses-telomerase-expression-by-inhibiting-sp1-binding-to-the-tert-promoter
#2
Deepa Rajagopalan, Amit Kumar Pandey, Magdalene Claire Xiuzhen, Kwok Kin Lee, Shainan Hora, Yanzhou Zhang, Boon Haow Chua, Hui Si Kwok, Shreshtha Sailesh Bhatia, Lih Wen Deng, Daniel G Tenen, Dennis Kappei, Sudhakar Jha
HIV1-TAT interacting protein (TIP60) is a haploinsufficient tumor suppressor. However, the potential mechanisms endowing its tumor suppressor ability remain incompletely understood. It plays a vital role in virus-induced cancers where TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6 which in turn destabilizes TIP60. This intrigued us to identify the role of TIP60, in the context of a viral infection, where it is targeted by oncoproteins. Through an array of molecular biology techniques such as Chromatin immunoprecipitation, expression analysis and mass spectrometry, we establish the hitherto unknown role of TIP60 in repressing the expression of the catalytic subunit of the human telomerase complex, TERT, a key driver for immortalization...
October 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29042578/%C3%AE-defensin-1-expression-in-hcv-infected-liver-liver-cancer-an-important-role-in-protecting-hcv-progression-and-liver-cancer-development
#3
Yue-Ming Ling, Jin-Yu Chen, Libin Guo, Chen-Yi Wang, Wen-Ting Tan, Qing Wen, Shu-Dong Zhang, Guo-Hong Deng, Yao Lin, Hang Fai Kwok
β-defensin family plays a role in host defense against viral infection, however its role in HCV infection is still unknown. In this study, we demonstrated that β-defensin 1 was significantly reduced in HCV-infected liver specimens. Treatment with interferon and ribavirin upregulated β-defensin-1, but not other β-defensin tested, with the extent and duration of upregulation associated with treatment response. We investigated β-defensin family expression in liver cancer in publicly available datasets and found that among all the β-defensins tested, only β-defensin 1 was significantly downregulated, suggesting β-defensin 1 plays a crucial role in liver cancer development...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29039460/characterization-of-tree-shrew-tupaia-belangeri-interleukin-6-and-its-expression-pattern-in-response-to-exogenous-challenge
#4
Yuanyuan Han, Xiaomei Sun, Dexuan Kuang, Pinfen Tong, Caixia Lu, Wenguang Wang, Na Li, Yang Chen, Xiaoping Wang, Jiejie Dai, Huatang Zhang
Tree shrews, one of the closest relatives of primates, have attracted increasing attention as a model of human diseases, particularly for viral infections. As the first line of defense against microbial pathogens, the innate immune system is crucial in tree shrews. Interleukin-6 (IL-6) is important in the pathophysiology of infection, inflammation and cancer, where it promotes disease development or sustains immune reactions. The present study aimed to obtain further insight into the tree shrew IL-6 (tsIL-6) system, and the function of tsIL-6 in the antiviral and antibacterial response...
October 2, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29038121/targeting-il-10-family-cytokines-for-the-treatment-of-human-diseases
#5
Xiaoting Wang, Kit Wong, Wenjun Ouyang, Sascha Rutz
Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses during host defense but also in autoimmune disorders, inflammatory diseases, and cancer. Although IL-10 itself primarily acts on leukocytes and has potent immunosuppressive functions, other family members preferentially target nonimmune compartments, such as tissue epithelial cells, where they elicit innate defense mechanisms to control viral, bacterial, and fungal infections, protect tissue integrity, and promote tissue repair and regeneration...
October 16, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#6
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033288/the-therapeutic-antibody-lm609-selectively-inhibits-ligand-binding-to-human-%C3%AE-v%C3%AE-3-integrin-via-steric-hindrance
#7
Andrew J Borst, Zachary M James, William N Zagotta, Mark Ginsberg, Felix A Rey, Frank DiMaio, Marija Backovic, David Veesler
The LM609 antibody specifically recognizes αVβ3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for αVβ3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of αVβ3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for αVβ3...
October 7, 2017: Structure
https://www.readbyqxmd.com/read/29032202/pact-is-required-for-mda5-mediated-immunoresponses-triggered-by-cardiovirus-infection-via-interaction-with-lgp2
#8
Masahiko Miyamoto, Akihiko Komuro
Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of Cardiovirus-infected cells and activate innate immune responses. Here, we evaluated whether the double-stranded RNA-binding protein PACT plays a role in this anti-viral response to further elucidate the mechanism. Immunoprecipitation experiments demonstrated that PACT interacts with LGP2 and that this interaction is enhanced by encephalomyocarditis virus (EMCV) infection...
October 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29029939/a-novel-therapeutic-vaccine-composed-of-a-rearranged-human-papillomavirus-type-16-e6-e7-fusion-protein-and-fms-like-tyrosine-kinase-3-ligand-induces-cd8-t-cell-responses-and-antitumor-effect
#9
Jianqiang Li, Si Chen, Jun Ge, Feng Lu, Sulin Ren, Zhiqiang Zhao, Xiuying Pu, Xiaoxiao Chen, Jiaojiao Sun, Yueqing Gu
The development of cervical cancer is mainly caused by infection with high risk genotypes of human papillomavirus, particularly type 16 (HPV16), which accounts for more than 50% of cervical cancer. The two early viral oncogenes, E6 and E7, are continuously expressed in cervical cancer cells and are necessary to maintain the malignant cellular phenotype, thus providing ideal targets for immunotherapy of cervical cancer. In this study, a novel vaccine strategy was developed based on a rationally shuffled HPV16 E6/E7 fusion protein, the addition of Fms-like tyrosine kinase-3 ligand (Flt3L) or the N domain of calreticulin (NCRT), and the usage of a CpG adjuvant...
October 10, 2017: Vaccine
https://www.readbyqxmd.com/read/29027878/are-prophylactic-antibiotic-agents-indicated-in-anorectal-surgery-for-patients-with-human-immunodeficiency-virus
#10
Shaivi A Patel, Robert J Kucejko, Edward A Fazendin, Juan L Poggio
BACKGROUND: With increased survival among patients with human immunodeficiency virus (HIV), surgeons have been seeing more cases of anal dysplasia and cancer. There is, however, no data on the incidence of surgical site infections (SSIs) in HIV-positive patients undergoing elective anorectal procedures, nor on the administration of prophylactic antibiotic agents. We reviewed a HIV-positive population that has undergone elective anorectal biopsy of areas of dysplasia observed on office anoscopy to assess the need for antibiotic prophylaxis...
October 13, 2017: Surgical Infections
https://www.readbyqxmd.com/read/29027233/dysregulated-cellular-functions-and-cell-stress-pathways-provide-critical-cues-for-activating-and-targeting-natural-killer-cells-to-transformed-and-infected-cells
#11
REVIEW
David H Raulet, Assaf Marcus, Laurent Coscoy
Natural killer (NK) cells recognize and kill cancer cells and infected cells by engaging cell surface ligands that are induced preferentially or exclusively on these cells. These ligands are recognized by activating receptors on NK cells, such as NKG2D. In addition to activation by cell surface ligands, the acquisition of optimal effector activity by NK cells is driven in vivo by cytokines and other signals. This review addresses a developing theme in NK cell biology: that NK-activating ligands on cells, and the provision of cytokines and other signals that drive high effector function in NK cells, are driven by abnormalities that arise from transformation or the infected state...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29026157/bortezomib-promotes-khsv-and-ebv-lytic-cycle-by-activating-jnk-and-autophagy
#12
Marisa Granato, Maria Anele Romeo, Mariangela Sara Tiano, Roberta Santarelli, Roberta Gonnella, Maria Saveria Gilardini Montani, Alberto Faggioni, Mara Cirone
KSHV and EBV are gammaherpesviruses strictly linked to human cancers. Even if the majority of cancer cells harbor a latent infection, the few cells that undergo viral replication may contribute to the pathogenesis and maintenance of the virus-associated malignancies. Cytotoxic drugs used for the therapies of cancers harboring virus-infection often have, as side effect, the activation of viral lytic cycle. Therefore it is important to investigate whether they affect viral reactivation and understand the underlying mechanisms involved...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024739/direct-antiviral-agents-daas-a-new-age-in-the-treatment-of-hepatitis-c-virus-infection
#13
REVIEW
Ulrich Spengler
Hepatitis C virus (HCV) is a global health problem, because infection frequently leads to chronic hepatitis C eventually progressing to liver cirrhosis and liver cancer. Improved insights into the HCV replication cycle and the role of HCV non-structural proteins has recently enabled to identify drugs directly acting on specific HCV target structures. Agents from three drug classes have been developed and approved by the health authorities. Combinations of two or more drugs from different classes achieve high (>90%) HCV clearance rates and are well tolerated...
October 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29021819/hiv-1-matrix-protein-p17-and-its-variants-promote-human-triple-negative-breast-cancer-cell-aggressiveness
#14
Francesca Caccuri, Francesca Giordano, Ines Barone, Pietro Mazzuca, Cinzia Giagulli, Sebastiano Andò, Arnaldo Caruso, Stefania Marsico
BACKGROUND: The introduction of cART has changed the morbidity and mortality patterns affecting HIV-infected (HIV(+)) individuals. The risk of breast cancer in HIV(+) patients has now approached the general population risk. However, breast cancer has a more aggressive clinical course and poorer outcome in HIV(+) patients than in general population, without correlation with the CD4 or virus particles count. These findings suggest a likely influence of HIV-1 proteins on breast cancer aggressiveness and progression...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29021521/tristetraprolin-inhibits-macrophage-il-27-induced-activation-of-antitumour-cytotoxic-t-cell-responses
#15
Qinghong Wang, Huan Ning, Hui Peng, Lin Wei, Rong Hou, Daniel F Hoft, Jianguo Liu
IFN-γ-producing cytotoxic T lymphocytes are essential for host defense against viral infection and cancer. Here we show that the RNA-binding tristetraprolin, encoded by Zfp36, is needed for CD8(+) T-cell production of IFN-γ in vivo. When activated in vitro, however, IFN-γ production by naive wild type and tristetraprolin-deficient CD8(+) T-cells is comparable. IL-27 is overproduced by tristetraprolin-deficient macrophages and increased systemically in tristetraprolin-deficient mice. Tristetraprolin suppresses IL-27 production by promoting p28 mRNA degradation...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018115/kaposi-s-sarcoma-associated-herpesvirus-increases-pd-l1-and-proinflammatory-cytokine-expression-in-human-monocytes
#16
Kurtis M Host, Sarah R Jacobs, John A West, Zhigang Zhang, Lindsey M Costantini, Charles M Stopford, Dirk P Dittmer, Blossom Damania
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with the human malignancy Kaposi's sarcoma and the lymphoproliferative disorders primary effusion lymphoma and multicentric Castleman's disease. KSHV establishes lytic infection of monocytes in vivo, which may represent an important cellular reservoir during KS disease progression. KS tumors consist of latently infected endothelial cells; however, lytic phase gene products are important for KS onset. Early KS lesion progression is driven by proinflammatory cytokines supplied by immune cell infiltrates including T cells and monocytes...
October 10, 2017: MBio
https://www.readbyqxmd.com/read/29017974/vectofusin-1-a-potent-peptidic-enhancer-of-viral-gene-transfer-forms-ph-dependent-%C3%AE-helical-nanofibrils-concentrating-viral-particles
#17
Louic S Vermeer, Loic Hamon, Alicia Schirer, Michel Schoup, Jérémie Cosette, Saliha Majdoul, David Pastré, Daniel Stockholm, Nathalie Holic, Petra Hellwig, Anne Galy, David Fenard, Burkhard Bechinger
Gene transfer using lentiviral vectors has therapeutic applications spanning from monogenic and infectious diseases to cancer. Such gene therapy has to be improved by enhancing the levels of viral infection of target cells and/or reducing the amount of lentivirus for greater safety and reduced costs. Vectofusin-1, a recently developed cationic amphipathic peptide with a pronounced capacity to enhance such viral transduction, strongly promotes the entry of several retroviral pseudotypes into target cells when added to the culture medium...
October 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29017269/cancer-attributable-mortality-among-people-with-treated-human-immunodeficiency-virus-infection-in-north-america
#18
Eric A Engels, Elizabeth L Yanik, Willian Wheeler, M John Gill, Meredith S Shiels, Robert Dubrow, Keri N Althoff, Michael J Silverberg, John T Brooks, Mari M Kitahata, James J Goedert, Surbhi Grover, Angel M Mayor, Richard D Moore, Lesley S Park, Anita Rachlis, Keith Sigel, Timothy R Sterling, Jennifer E Thorne, Ruth M Pfeiffer
Background: Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. Methods: We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer...
August 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29016628/hazardous-air-pollutants-and-primary-liver-cancer-in-texas
#19
Luca Cicalese, Giuseppe Curcuru, Mauro Montalbano, Ali Shirafkan, Jeremias Georgiadis, Cristiana Rastellini
The incidence of hepatocellular carcinoma (HCC), the most common primary liver cancer, is increasing in the US and tripled during the past two decades. The reasons for such phenomenon remain poorly understood. Texas is among continental states with the highest incidence of liver cancer with an annual increment of 5.7%. Established risk factors for HCC include Hepatitis B and C (HBV, HCV) viral infection, alcohol, tobacco and suspected risk factors include obesity and diabetes. While distribution of these risk factors in the state of Texas is similar to the national data and homogeneous, the incidence of HCC in this state is exceptionally higher than the national average and appears to be dishomogeneous in various areas of the state suggesting that other non-recognized risk factors might play a role...
2017: PloS One
https://www.readbyqxmd.com/read/28994707/why-human-papillomavirus-acute-infections-matter
#20
REVIEW
Samuel Alizon, Carmen Lía Murall, Ignacio G Bravo
Most infections by human papillomaviruses (HPVs) are `acute', that is non-persistent. Yet, for HPVs, as for many other oncoviruses, there is a striking gap between our detailed understanding of chronic infections and our limited data on the early stages of infection. Here we argue that studying HPV acute infections is necessary and timely. Focusing on early interactions will help explain why certain infections are cleared while others become chronic or latent. From a molecular perspective, descriptions of immune effectors and pro-inflammatory pathways during the initial stages of infections have the potential to lead to novel treatments or to improved handling algorithms...
October 10, 2017: Viruses
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