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Immunopathology of viral

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https://www.readbyqxmd.com/read/29329934/application-of-our-understanding-of-pathogenesis-of-herpetic-stromal-keratitis-for-novel-therapy
#1
Naveen K Rajasagi, Barry T Rouse
HSV-1 ocular infection can cause herpes stromal keratitis (SK), an immunopathological lesion. Frequent recurrences can lead to progressive corneal scaring which can result in vision impairment if left untreated. Currently, the acute and epithelial forms of SK are usually controlled using anti-viral drugs. However, chronic forms of SK which are inflammatory in nature, require the addition of a topical corticosteroid to the anti-viral treatment regimen. In this review, we highlight the essential events involved in SK pathogenesis which can be targeted for improved therapy...
January 9, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29312814/on-revealing-the-gene-targets-of-ebola-virus-micrornas-involved-in-the-human-skin-microbiome
#2
Pei-Chun Hsu, Bin-Hao Chiou, Chun-Ming Huang
Ebola virus, a negative-sense single-stranded RNA virus, causes severe viral hemorrhagic fever and has a high mortality rate. Histopathological and immunopathological analyses of Ebola virus have revealed that histopathological changes in skin tissue are associated with various degrees of endothelial cell swelling and necrosis. The interactions of microbes within or on a host are a crucial for the skin immune shield. The discovery of microRNAs (miRNAs) in Ebola virus implies that immune escape, endothelial cell rupture, and tissue dissolution during Ebola virus infection are a result of the effects of Ebola virus miRNAs...
2018: PeerJ
https://www.readbyqxmd.com/read/29311359/the-effects-of-dendritic-cell-hypersensitivity-on-persistent-viral-infection
#3
Jennifer S Tsau, Xin Huang, Chen-Yen Lai, Stephen M Hedrick
Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29300777/internal-genes-of-a-highly-pathogenic-h5n1-influenza-virus-determine-high-viral-replication-in-myeloid-cells-and-severe-outcome-of-infection-in-mice
#4
Hui Li, Konrad C Bradley, Jason S Long, Rebecca Frise, Jonathan W Ashcroft, Lorian C Hartgroves, Holly Shelton, Spyridon Makris, Cecilia Johansson, Bin Cao, Wendy S Barclay
The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load...
January 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29295868/the-immunoproteasome-specific-inhibitor-onx-0914-reverses-susceptibility-to-acute-viral-myocarditis
#5
Nadine Althof, Carl Christoph Goetzke, Meike Kespohl, Karolin Voss, Arnd Heuser, Sandra Pinkert, Ziya Kaya, Karin Klingel, Antje Beling
Severe heart pathology upon virus infection is closely associated with the immunological equipment of the host. Since there is no specific treatment available, current research focuses on identifying new drug targets to positively modulate predisposing immune factors. Utilizing a murine model with high susceptibility to coxsackievirus B3-induced myocarditis, this study describes ONX 0914-an immunoproteasome-specific inhibitor-as highly protective during severe heart disease. Represented by reduced heart infiltration of monocytes/macrophages and diminished organ damage, ONX 0914 treatment reversed fulminant pathology...
January 2, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29286160/identification-and-characterization-of-epitopes-from-influenza-a-virus-hemagglutinin-that-induce-broadly-cross-reactive-antibodies
#6
Yuan Li, Hanyu Hu, Zongli Qi, Jingying Sun, Yan Li, Qing Feng, Chunyan Guo, Haifang Wang, Penghua Zhao, Yang Liu, Xiangrong Zhao, Guanghua Wang, Hai Zhang, Libin Liu, Jun Hu
Influenza is the most common infectious disease and is caused by influenza A virus (IAV) infection. Hemagglutinin (HA) is an important viral protein of influenza A and is a major component of current IAV vaccines. The side effects associated with IAV vaccination are well studied; however, the HA‑induced immunopathological changes have remained largely elusive. The primary objective of the present study was to determine the tissue cross‑reactive epitopes of HA proteins. Monoclonal antibodies (McAbs) were generated according to traditional methods using purified HA proteins from influenza vaccine lysates...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29273643/plasmacytoid-dendritic-cells-protect-from-viral-bronchiolitis-and-asthma-through-semaphorin-4a-mediated-t-reg-expansion
#7
Jason P Lynch, Rhiannon B Werder, Zhixuan Loh, Md Al Amin Sikder, Bodie Curren, Vivian Zhang, Matthew J Rogers, Katie Lane, Jennifer Simpson, Stuart B Mazzone, Kirsten Spann, John Hayball, Kerrilyn Diener, Mark L Everard, Christopher C Blyth, Christian Forstner, Paul G Dennis, Nida Murtaza, Mark Morrison, Páraic Ó Cuív, Ping Zhang, Ashraful Haque, Geoffrey R Hill, Peter D Sly, John W Upham, Simon Phipps
Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a)...
December 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29258535/lytic-viral-replication-and-immunopathology-in-a-cytomegalovirus-induced-mouse-model-of-secondary-hemophagocytic-lymphohistiocytosis
#8
Ellen Brisse, Maya Imbrechts, Tania Mitera, Jessica Vandenhaute, Carine H Wouters, Robert Snoeck, Graciela Andrei, Patrick Matthys
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder caused by unbridled activation of T cells and macrophages, culminating in a life-threatening cytokine storm. A genetic and acquired subtype are distinguished, termed primary and secondary HLH, respectively. Clinical manifestations of both forms are frequently preceded by a viral infection, predominantly with herpesviruses. The exact role of the viral infection in the development of the hemophagocytic syndrome remains to be further elucidated...
December 19, 2017: Virology Journal
https://www.readbyqxmd.com/read/29243132/hiv-associated-opsoclonus-myoclonus-ataxia-syndrome-early-infection-immune-reconstitution-syndrome-or-secondary-to-other-diseases-case-report-and-literature-review
#9
Bruno F Guedes, Márcio A A Vieira Filho, Clarice Listik, Rafael B Carra, Cristiane B Pereira, Emanuelle R da Silva, Hélio R Gomes, José E Vidal
Opsoclonus-myoclonus-ataxia (OMA) syndrome is a debilitating autoimmune neurological disorder. Post-infectious opsoclonus-myoclonus-ataxia syndrome has been described with varying bacterial, spirochetal, and viral infections including several patients with HIV. However, specific immunopathological mechanisms that may lead to opsoclonus-myoclonus in HIV-positive patients are unknown.We report a case of HIV-associated opsoclonus-myoclonus and early HIV infection. A review of published literature shows opsoclonus-myoclonus can occur during early infection, in immune reconstitution syndrome or in association with other infections, especially tuberculosis...
December 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29230219/functional-impairment-of-mononuclear-phagocyte-system-by-the-human-respiratory-syncytial-virus
#10
REVIEW
Karen Bohmwald, Janyra A Espinoza, Raúl A Pulgar, Evelyn L Jara, Alexis M Kalergis
The mononuclear phagocyte system (MPS) comprises of monocytes, macrophages (MΦ), and dendritic cells (DCs). MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV). The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29201154/lymphatic-system-and-gut-microbiota-affect-immunopathology-of-neuroinflammatory-diseases-including-multiple-sclerosis-neuromyelitis-optica-and-alzheimer-s-disease
#11
Ikuo Tsunoda
Microbial infections lead to neurological damages either by direct infection in the nervous tissues or by uncontrolled immune responses (immunopathology). For example, in Zika virus infection, microcephaly can be caused by the former, i.e., direct viral infection in the brain, while Guillain-Barré syndrome (GBS) seems to be antibody-mediated immunopathology. Although a variety of factors affect immunopathology, two essential systems maintaining whole-body homeostasis had long been neglected: 1) the lymphatic system and 2) microbiota...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/29194124/humanized-mouse-models-to-study-pathophysiology-and-treatment-of-hiv-infection
#12
Guillemette Masse-Ranson, Hugo Mouquet, James P Di Santo
PURPOSE OF REVIEW: Immunodeficient mice that lack all lymphocyte subsets and have phagocytic cells that are tolerant of human cells can be stably xenografted with human hematopoietic stem cell as well as other human tissues (fetal liver and thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and their specialized subsets as well as a variety of myeloid cells (dendritic cell, monocytes, and macrophages) thereby providing a small animal model in which to interrogate human immune responses to infection...
November 30, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29186689/lymphocytes-negatively-regulate-nk-cell-activity-via-qa-1b-following-viral-infection
#13
Haifeng C Xu, Jun Huang, Aleksandra A Pandyra, Elisabeth Lang, Yuan Zhuang, Christine Thöns, Jörg Timm, Dieter Häussinger, Marco Colonna, Harvey Cantor, Karl S Lang, Philipp A Lang
NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29145733/harnessing-novel-imaging-approaches-to-guide-hiv-prevention-and-cure-discoveries-a-national-institutes-of-health-and-global-hiv-vaccine-enterprise-2017-meeting-report
#14
Brigitte Elisabeth Sanders-Beer, Yegor Voronin, David McDonald, Anjali Singh
Advances in imaging technologies have greatly increased our understanding of cellular and molecular interactions in humans and their corresponding animal models of infectious diseases. In the HIV/SIV field, imaging has provided key insights into mucosal viral transmission, local and systemic virus spread, host-virus dynamics, and chronic inflammation/immune activation and the resultant immunopathology. Recent developments in imaging applications are yielding physical, spatial, and temporal measurements to enhance insight into biological functions and disease processes, while retaining important cellular, microenvironmental, organ and intact organism contextual details...
November 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29127663/poly-i-c-priming-exacerbates-cecal-ligation-and-puncture-induced-polymicrobial-sepsis-in-mice
#15
Deepika Sharma, Ankit Malik, Nandakumar Packiriswamy, Michael D Steury, Narayanan Parameswaran
Sepsis continues to be a major healthcare issue with one of the highest mortality rates in intensive care units. Toll-like receptors are pattern recognition receptors that are intricately involved in the pathogenesis of sepsis. TLR3 is a major receptor for double-stranded RNA and is largely associated with immunity to viral infection. In this study, we examined the role of TLR3 priming in the immunopathology of sepsis using cecal-ligation and puncture (CLP) model of sepsis in mice. Mice injected with vehicle or poly(I:C) were subjected to sham or CLP surgery and various parameters of sepsis, including mortality, inflammation, and bacterial clearance were assessed...
November 10, 2017: Inflammation
https://www.readbyqxmd.com/read/29108855/hiv-patients-healthy-aging-and-transplant-recipients-can-reveal-the-hidden-footprints-of-cmv
#16
REVIEW
Shelley Waters, Emily Brook, Silvia Lee, Riwanti Estiasari, Ibnu Ariyanto, Patricia Price
Cytomegalovirus (CMV) is a β-herpesvirus. Latent infections are common in all populations. However age-associated increases in levels of CMV-reactive antibody are testament to a repeated reactivations and periods of viral replication. CMV has been associated with several diseases of aging, including vasculopathy and neurocognitive impairment. These conditions occur at a younger age in persons with particularly high burdens of CMV - transplant recipients and people living with HIV. Here we define the "clinical footprints" as immunopathologies triggered by CMV that develop over many years...
November 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29103421/a-neuroprimer-principles-of-central-nervous-system-immunity
#17
Gregory P Owens
Despite longstanding perceptions, robust innate and adaptive immune responses occur within the central nervous system (CNS) in response to infection and tissue damage. Although necessary to control infection, immune responses can lead to severe CNS pathology in the context of both viral infection and autoimmunity. Research into how the central nervous and immune systems communicate has accelerated over the past 20 years leading to a better understanding of pathways controlling immune activation and neuroinflammation that have guided the approval of new disease-modifying therapies to treat CNS immunopathology, particularly the inflammatory demyelinating disease multiple sclerosis...
August 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/29076066/recombinant-baculovirus-based-vaccine-expressing-m2-protein-induces-protective-cd8-t-cell-immunity-against-respiratory-syncytial-virus-infection
#18
Jeong-Yoon Lee, Jun Chang
Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract disease in infants, young children, immunocompromised individuals, and the elderly. However, despite ongoing efforts to develop an RSV vaccine, there is still no authorized RSV vaccine for humans. Baculovirus has attracted attention as a vaccine vector because of its ability to induce a high level of humoral and cellular immunity, low cytotoxicity against various antigens, and biological safety for humans. In this study, we constructed a recombinant baculovirus- based vaccine expressing the M2 protein of RSV under the control of cytomegalovirus promoter (Bac_RSVM2) to induce CD8(+) T-cell responses which play an important role in viral clearance, and investigated its protective efficacy against RSV infection...
November 2017: Journal of Microbiology / the Microbiological Society of Korea
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
#19
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/29033929/immunity-and-fibrogenesis-the-role-of-th17-il-17-axis-in-hbv-and-hcv-induced-chronic-hepatitis-and-progression-to-cirrhosis
#20
REVIEW
Feliciano Chanana Paquissi
Cirrhosis is a common final pathway for most chronic liver diseases; representing an increasing burden worldwide and is associated with increased morbidity and mortality. Current evidence has shown that, after an initial injury, the immune response has a significant participation in the ongoing damage, and progression from chronic viral hepatitis (CVH) to cirrhosis, driving the activation and maintenance of main fibrogenic pathways. Among immune deregulations, those related to the subtype 17 of T helper lymphocytes (Th17)/interleukin-17 (IL-17) axis have been recognized as key immunopathological and prognostic elements in patients with CVH...
2017: Frontiers in Immunology
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