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Pathogenesis of viral infection of the lungs

Xiangjie Sun, Hui Zeng, Amrita Kumar, Jessica A Belser, Taronna R Maines, Terrence M Tumpey
: A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. Here, we found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses...
October 5, 2016: Journal of Virology
Jamie Rylance, Grace Mchugh, John Metcalfe, Hilda Mujuru, Kusum Nathoo, Stephanie Wilmore, Sarah Rowland-Jones, Edith Majonga, Katharina Kranzer, Rashida A Ferrand
OBJECTIVE: Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function, and exercise capacity among older children established on ART, and an age-matched HIV-uninfected group. DESIGN: A cross-sectional study in Zimbabwe of: 1) HIV-infected children aged 6-16 years receiving ART for over six months; 2) HIV-uninfected children attending primary health clinics from the same area...
September 20, 2016: AIDS
Hong Zheng, Wei Dai, Arthur Kwok Leung Cheung, Josephine Mun Yee Ko, Rebecca Kan, Bonnie Wing Yan Wong, Merrin Man Long Leong, Mingdan Deng, Tommy Chin Tung Kwok, Jimmy Yu-Wai Chan, Dora Lai-Wan Kwong, Anne Wing-Mui Lee, Wai Tong Ng, Roger Kai Cheong Ngan, Chun Chung Yau, Stewart Tung, Victor Ho-Fun Lee, Ka-On Lam, Chung Kong Kwan, Wing Sum Li, Stephen Yau, Kwok-Wah Chan, Maria Li Lung
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3 Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Katrijn Neyt, Corine H GeurtsvanKessel, Kim Deswarte, Hamida Hammad, Bart N Lambrecht
Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT...
2016: Frontiers in Immunology
Mary K McCarthy, Danielle H Malitz, Caitlyn T Molloy, Megan C Procario, Kaitlyn E Greiner, Luna Zhang, Ping Wang, Sharlene M Day, Saul R Powell, Jason B Weinberg
The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner...
November 2016: Virology
Ryan M Reddinger, Nicole R Luke-Marshall, Anders P Hakansson, Anthony A Campagnari
UNLABELLED: Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease. S. aureus is a major source of severe secondary bacterial pneumonia after influenza A virus infection, which causes widespread morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is well established, the mechanisms behind the transition from asymptomatic colonization to invasive staphylococcal disease following viral infection remains unknown...
2016: MBio
Victoria A Meliopoulos, Lee-Ann Van de Velde, Nicholas C Van de Velde, Erik A Karlsson, Geoff Neale, Peter Vogel, Cliff Guy, Shalini Sharma, Susu Duan, Sherri L Surman, Bart G Jones, Michael D L Johnson, Catharine Bosio, Lisa Jolly, R Gisli Jenkins, Julia L Hurwitz, Jason W Rosch, Dean Sheppard, Paul G Thomas, Peter J Murray, Stacey Schultz-Cherry
The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI...
August 2016: PLoS Pathogens
Christin Peteranderl, Susanne Herold, Carole Schmoldt
Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact...
August 2016: Seminars in Respiratory and Critical Care Medicine
Wentao Cai, Sunrui Chen, Yongtao Li, Anding Zhang, Hongbo Zhou, Huanchun Chen, Meilin Jin
Traditional Chinese medicine (TCM) has been an excellent treasury for centuries' accumulation of clinical experiences, which deserves to be tapped for potential drugs and improved using modern scientific methods. 14-Deoxy-11,12-didehydroandrographolide (DAP), a major component of an important TCM named Andrographis paniculata, with non-toxic concentration of 1000 mg/kg/day, effectively reduced the mortality and weight loss of mice lethally challenged with A/chicken/Hubei/327/2004 (H5N1) or A/PR/8/34 (H1N1) influenza A viruses (IAV) when initiated at 4 h before infection, or A/duck/Hubei/XN/2007 (H5N1) when initiated at 4 h or 48 h before infection, or 4 h post-infection (pi)...
September 2016: Antiviral Research
Susanna L Lamers, Rebecca Rose, Ekaterina Maidji, Melissa Agsalda-Garcia, David J Nolan, Gary B Fogel, Marco Salemi, Debra L Garcia, Paige Bracci, William Yong, Deborah Commins, Jonathan Said, Negar Khanlou, Charles H Hinkin, Miguel Valdes Sueiras, Glenn Mathisen, Suzanne Donovan, Bruce Shiramizu, Cheryl A Stoddart, Michael S McGrath, Elyse J Singer
UNLABELLED: HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort...
October 15, 2016: Journal of Virology
Jung-Ah Lee, Yu-Ri Oh, Min-A Hwang, Joong-Bok Lee, Seung-Yong Park, Chang-Seon Song, In-Soo Choi, Sang-Won Lee
The porcine respiratory disease complex (PRDC) caused by numerous bacterial and viral agents has a great impact on pig industry worldwide. Although Mycoplasma hyorhinis (Mhr) has been frequently isolated from lung lesions from pigs with PRDC, the pathological importance of Mhr may have been underestimated. In this study, 383 serum samples obtained from seven herds with a history of PRDC were tested for specific antibodies to Mhr, Mycoplasma hyopneumoniae (Mhp), and porcine reproductive and respiratory syndrome virus (PRRSV)...
September 2016: Veterinary Immunology and Immunopathology
Carla Bianca Luena Victorio, Yishi Xu, Qimei Ng, Beng Hooi Chua, Sylvie Alonso, Vincent T K Chow, Kaw Bing Chua
Enterovirus 71 (EV-A71) is a neurotropic virus that sporadically causes fatal neurologic illness among infected children. Animal models of EV-A71 infection exist, but they do not recapitulate in animals the spectrum of disease and pathology observed in fatal human cases. Specifically, neurogenic pulmonary oedema (NPE)-the main cause of EV-A71 infection-related mortality-is not observed in any of these models. This limits their utility in understanding viral pathogenesis of neurologic infections. We report the development of a mouse model of EV-A71 infection displaying NPE in severely affected animals...
2016: Scientific Reports
Angel S Galabov, Milka Mileva, Lora Simeonova, Galina Gegova
BACKGROUND: Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis-viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. METHODS: After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2...
August 2015: Antiviral Chemistry & Chemotherapy
Khadija Khataby, Faouzi Kichou, Chafiqa Loutfi, My Mustapha Ennaji
BACKGROUND: Avian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported. 40 one-day-old specific pathogen free chickens were divided randomly into four groups...
2016: BMC Veterinary Research
Man He, Min Wang, Ying Huang, Wenju Peng, Zizheng Zheng, Ningshao Xia, Jian Xu, Deying Tian
Hepatitis E virus (HEV) genotype 1 infection is common and can emerge as outbreaks in developing areas, thus posing a threat to public health. However, due to the absence of feasible animal models, the mechanism of HE pathogenesis remains obscure. The HEV pathogenic mechanism has been suggested to be mediated by the immune system and not by direct viral duplication. We firstly discovered that the open reading frame 3 (ORF3) protein of genotype 1 HEV downregulates TLR3-mediated NF-κB signaling in Human A549 Lung Epithelial Cells (A549 cells) which were exposed to different TLR agonists associated with viral nucleic acids...
2016: Scientific Reports
S Puglisi, S E Torrisi, R Giuliano, V Vindigni, C Vancheri
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause, occurring in adults, limited to the lungs and associated with the pathologic and radiologic pattern of usual interstitial pneumonia. Prognosis is poor, and most patients die of respiratory failure within 3 to 6 years from the onset of symptoms. Although our understanding of the pathogenesis of IPF has improved over the past two decades, the mechanisms responsible for this disorder have not been clearly defined. Aging is the single most important risk factor, but genetic, environmental, and diverse exogenous factors such as smoking, viral infections, chronic tissue injury (i...
June 2016: Seminars in Respiratory and Critical Care Medicine
Arwa Z Al-Riyami, Khalil Al-Farsi, Murtadha Al-Khabori, Mohammed Al-Huneini, Ibrahim Al-Hadabbi
Natural killer (NK) cell lymphoproliferative disorders are uncommon and the Epstein-Barr virus (EBV) plays an important aetiological role in their pathogenesis. We report a 20-year-old male with a chronic active EBV infection associated with a NK cell lymphoproliferative disorder which had an unusual indolent course. He presented to the Sultan Qaboos University Hospital in Muscat, Oman, in December 2011 with a history of intermittent fever and coughing. Examinations revealed generalised lymphadenopathy, hepatosplenomegaly, leukocytosis, transaminitis, diffuse bilateral lung infiltrates and bone marrow lymphocyte involvement...
May 2016: Sultan Qaboos University Medical Journal
Junji Yodoi, Hai Tian, Hiroshi Masutani, Hajime Nakamura
A 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-, human thioredoxin 1 (TRX) has demonstrated an excellent anti-inflammatory effect in various animal models. TRX is induced by various oxidative stress factors, including ultraviolet rays, radiation, oxidation, viral infections, ischemia reperfusion and anticancer agents, and are involved in the pathogenesis and progression of various diseases. We have demonstrated that systemic administration and transgenic overexpression of TRX is effective in a wide variety of in vivo inflammatory disease models, such as viral pneumonia, acute lung injury, chronic obstructive pulmonary disease, indomethacin-induced gastric injury, and dermatitis...
April 1, 2016: Archives of Biochemistry and Biophysics
Yan Yang, Hong Tang
Influenza A virus (IAV) infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular (endothelial cells and platelets) and protein (coagulation factors, anticoagulants and fibrinolysis proteases) components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis...
July 2016: Cellular & Molecular Immunology
Samuel Philip Nobs, Christoph Schneider, Alex Kaspar Heer, Jatta Huotari, Ari Helenius, Manfred Kopf
Phosphoinositide-3-kinases have been shown to be involved in influenza virus pathogenesis. They are targeted directly by virus proteins and are essential for efficient viral replication in infected lung epithelial cells. However, to date the role of PI3K signaling in influenza infection in vivo has not been thoroughly addressed. Here we show that one of the PI3K subunits, p110γ, is in fact critically required for mediating the host's antiviral response. PI3Kγ deficient animals exhibit a delayed viral clearance and increased morbidity during respiratory infection with influenza virus...
March 2016: PLoS Pathogens
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