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Interferons and viral infections

Mohsan Ullah Goraya, Fozia Ziaghum, Shilong Chen, Ali Raza, Ye Chen
Classical swine fever virus (CSFV) infection causes mild to severe diseases among pigs, depending on the age and immune status of the host and viral strains. CSFV targets various cells, including macrophages and conventional and plasmacytoid dendritic cells. Classical swine fever is one of the most devastating diseases of pigs which leads to high morbidity and mortality, and causes significant economic loss worldwide. In response to infection with CSFV, host innate immune system eliminates the virus by recognizing specific viral molecules via distinct cellular pattern recognition receptors...
April 12, 2018: Microbial Pathogenesis
Elisa Vicenzi, Guido Poli
Infection of target cells by the human immunodeficiency virus type-1 (HIV-1) is hampered by constitutively expressed host cell proteins preventing or curtailing virus replication and therefore defined as "restriction factors". Among them, members of the tripartite motif (TRIM) family have emerged as important players endowed with both antiviral effects and modulatory capacity of the innate immune response. TRIM5α and TRIM19 (i.e. promyelocytic leukemia, PML) are among the best-characterized family members; however, in this review we will focus on the potential role of another family member, i...
February 10, 2018: Cytokine & Growth Factor Reviews
Federico Perdomo-Celis, Natalia A Taborda, Maria T Rugeles
BACKGROUND: Despite advances made with the highly active anti-retroviral therapy (HAART) in the control of the human immunodeficiency virus 1 (HIV) infection, a cure has not been achieved due to the persistence of viral reservoirs. The major HIV reservoirs remain in the lymphoid follicles due to, among other factors, the partial absence of CD8T-cells in these structures. Recently, lymphoid follicle-confined and circulating CD8T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, possessing antiviral mechanisms which could help to control HIV replication...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Shintaro Yamada, Masayuki Shimojima, Ryo Narita, Yuta Tsukamoto, Hiroki Kato, Masayuki Saijo, Takashi Fujita
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a tick-borne phlebovirus of the family Bunyaviridae , the SFTS virus (SFTSV). Wild type and type I interferon (IFN-I) receptor 1-deficient (IFNAR1-/- ) mice have been established as non-lethal and lethal models of SFTSV infection, respectively. However, the mechanisms of IFN-I production in vivo and the factors causing the lethal disease are not well understood. Using bone marrow chimeric mice, we found that IFN-I signaling in hematopoietic cells was essential for survival from lethal SFTSV infection...
April 11, 2018: Journal of Virology
Bo Feng, Qian Zhang, Jianfang Wang, Hong Dong, Xiang Mu, Ge Hu, Tao Zhang
IFIT1 (also known as ISG56) is a member of the interferoninducible protein with tetratricopeptide repeats (IFITs) family. IFITs are strongly induced by type I interferon (IFN), doublestranded RNA and virus infection. Here, we investigated IFIT1 expression in human umbilical vein endothelial cells (HUVECs) and in human bronchus epithelial cells (BEAS-2Bs) induced by the H9N2 virus and inactivated viral particle at different time points. We also investigated the effect of H9N2 virus and viral particle infection on IFN-α/β production, and assessed whether hemagglutinin or neuraminidase protein induced IFIT1 expression...
April 5, 2018: Molecules and Cells
Roman Radetskyy, Aïcha Daher, Anne Gatignol
The induction of hundreds of Interferon Stimulated Genes (ISGs) subsequent to virus infection generates an antiviral state that functions to restrict virus growth at multiple steps of their replication cycles. In the context of Human Immunodeficiency Virus-1 (HIV-1), ISGs also possess antiviral functions, but some ISGs show proapoptotic or proviral activity. One of the most studied ISGs, the RNA activated Protein Kinase (PKR), shuts down the viral protein synthesis upon activation. HIV-1 has evolved to evade its inhibition by PKR through viral and cellular mechanisms...
March 26, 2018: Cytokine & Growth Factor Reviews
Isabel Pagani, Andrea Di Pietro, Alexandra Oteiza, Michela Ghitti, Nadir Mechti, Nadia Naffakh, Elisa Vicenzi
Influenza A viruses (IAVs) can cause zoonotic infections with pandemic potential when most of the human population is immunologically naive. After a pandemic, IAVs evolve to become seasonal in the human host by acquiring adaptive mutations. We have previously reported that the interferon (IFN)-inducible tripartite motif 22 (TRIM22) protein restricts the replication of seasonal IAVs by direct interaction with the viral nucleoprotein (NP), leading to its polyubiquitination and proteasomal degradation. Here we show that, in contrast to seasonal H1N1 IAVs, the 2009 pandemic H1N1 strain as well as H1N1 strains from the 1930s are resistant to TRIM22 restriction...
April 25, 2018: MSphere
Xiuqin Yang, Xiaoyan Jing, Yanfang Song, Caixia Zhang, Di Liu
IFN-induced protein with tetratricopeptide repeats 2 (IFIT2) plays important roles in host defense against viral infection as revealed by studies in humans and mice. However, little is known on porcine IFIT2 (pIFIT2). Here, we performed molecular cloning, expression profile, and transcriptional regulation analysis of pIFIT2. pIFIT2 gene, located on chromosome 14, is composed of two exons and have a complete coding sequence of 1407 bp. The encoded polypeptide, 468 aa in length, has three tetratricopeptide repeat motifs...
April 6, 2018: Molecular Biology Reports
Peter Le Souëf
Over the past year, studies into virus-induced wheeze in children have shifted towards investigations that examine the mechanisms by which respiratory viruses cause wheeze and an increase in studies examining the effects of novel interventions to reduce wheezing exacerbations. Studies on rhinovirus species (RV)-C infection have found that this is associated with a decrease in expression of CDHR3, the cellular receptor specific for this virus, and a decrease in interferon-β expression, both of which are likely to favour RV-C infection...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Shi-Fang Li, Jun-Jun Shao, Fu-Rong Zhao, Mei-Jiao Gong, Yin-Li Xie, Hui-Yun Chang, Yong-Guang Zhang
Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8...
April 2, 2018: International Immunopharmacology
Lucy Golden-Mason, Rachel H McMahan, Michael S Kriss, Alexandra L Kilgore, Linling Cheng, Rachael J Dran, Amanda Wieland, Hugo R Rosen
Chronic hepatitis C virus (HCV) infection is characterized by dysregulated natural killer (NK) cell responses. NKs play a critical role in achieving sustained responses to interferon (IFN)-α-based therapy. Rapid sustained HCV-RNA clearance is now achieved with direct-acting antivirals (DAAs). Studies of patients receiving first-wave DAAs suggest NK functional restoration. Here, we investigate the effect of mainstream DAA treatment on NKs. We collected a prospective cohort of male HCV genotype 1-infected patients treated with ledipasvir/sofosbuvir (n = 22)...
April 2018: Hepatology Communications
Karla Cervantes-Gracia, Holger Husi
Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammatory-demyelinating events in the central nervous system. Despite more than 40 years of MS research its aetiology remains unknown. This study aims to identify the most frequently reported and consistently regulated molecules in MS in order to generate molecular interaction networks and thereby leading to the identification of deregulated processes and pathways which could give an insight of the underlying molecular mechanisms of MS...
April 4, 2018: Scientific Reports
Sha Xie, Xin-Xin Chen, Songlin Qiao, Rui Li, Yangang Sun, Shuangfei Xia, Lin-Jian Wang, Xuegang Luo, Ruiguang Deng, En-Min Zhou, Gai-Ping Zhang
Once infected by viruses, cells can detect pathogen associated molecular patterns (PAMPs) on viral nucleic acid by host pattern recognition receptors (PRRs) to initiate the antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), characterized by reproductive failure in sows and respiratory diseases in pigs of different ages. To date, the sensing mechanism of PRRSV has not been elucidated. Here, we reported that the pseudoknot region residing in the 3' untranslated regions (UTR) of PRRSV genome, which has been proposed to regulate RNA synthesis and virus replication, was sensed as non-self by retinoic acid-inducible gene I (RIG-I) and Toll like receptor (TLR3) and strongly induced type I IFNs and interferon-stimulated genes (ISGs) in porcine alveolar macrophages (PAMs)...
April 4, 2018: Journal of Virology
Jin Tian, Yongxiang Liu, Xiaoxiao Liu, Xue Sun, Jikai Zhang, Liandong Qu
As a prevalent agent in cats, feline herpesvirus 1 (FHV-1) infection contributes to feline respiratory disease and acute and chronic conjunctivitis. FHV-1 can successfully evade the host innate immune response and persist for the lifetime of the cat. Several mechanisms of immune evasion by human herpesviruses have been elucidated, but the mechanism by FHV-1 remains unknown. In this study, we screened for FHV-1 ORFs responsible for inhibiting type I interferon (IFN) pathway with an IFN-β promoter reporter and an analysis of IFN-β mRNA levels in HEK 293T cells and CRFK feline cell line, and we identified the Ser/Thr kinase US3 as the most powerful inhibitor...
April 4, 2018: Journal of Virology
Qiang Guo, Jasper Fuk-Woo Chan, Vincent Kwok-Man Poon, Shipo Wu, Chris Chung-Sing Chan, Lihua Hou, Cyril Chik-Yan Yip, Changpeng Ren, Jian-Piao Cai, Mengsu Zhao, Anna Jinxia Zhang, Xiaohong Song, Kwok-Hung Chan, Busen Wang, Kin-Hang Kok, Yanbo Wen, Kwok-Yung Yuen, Wei Chen
Background: Zika virus (ZIKV) infection may be associated with severe complications and disseminated via both vector-borne and non-vector-borne routes. Adenovirus-vectored vaccines represent a favorable controlling measure for the ZIKV epidemic as they have been shown to be safe, immunogenic, and rapidly generable for other emerging viral infections. Evaluations of two previously reported adenovirus-vectored ZIKV vaccines were performed using non-lethal animal models and/or non-epidemic ZIKV strain...
March 29, 2018: Journal of Infectious Diseases
Shuliang Chen, Serena Bonifati, Zhihua Qin, Corine St Gelais, Karthik M Kodigepalli, Bradley S Barrett, Sun Hee Kim, Jenna M Antonucci, Katherine J Ladner, Olga Buzovetsky, Kirsten M Knecht, Yong Xiong, Jacob S Yount, Denis C Guttridge, Mario L Santiago, Li Wu
Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we show that SAMHD1 suppresses the innate immune responses to viral infections and inflammatory stimuli by inhibiting nuclear factor-κB (NF-κB) activation and type I interferon (IFN-I) induction...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Chandana Ray Das, Diptika Tiwari, Anita Dongre, Mohammad Aasif Khan, Syed Akhtar Husain, Anirudha Sarma, Sujoy Bose, Purabi Deka Bose
Multiple factors are associated with human papillomavirus (HPV) infection related cervical anomalies and its progression to cervical carcinoma (CaCx), but data vary with respect to the underlying HPV genotype and with population being studied. No data are available regarding the role of immunological imbalance in HPV infected CaCx pathogenesis from Northeast India, which has an ethnically distinct population, and was aimed to be addressed through this study. The study included 76 CaCx cases, 25 cervical intraepithelial neoplasia (CIN) cases, and 50 healthy female controls...
April 2, 2018: Viral Immunology
Jay R Radke, James L Cook
PURPOSE OF REVIEW: To provide an update on recent studies of human adenoviral (HAdV) infections and to explore the mechanisms of viral persistence and the role of persistent infection in disseminated disease in immunocompromised patients. RECENT FINDINGS: Human adenoviruses continue to be a problem in ophthalmology clinics and to cause periodic, limited, global outbreaks of respiratory disease. Ad14p1 remains in worldwide circulation and continues to result in miniepidemics of severe respiratory infections...
March 29, 2018: Current Opinion in Infectious Diseases
Yung Jin Jeon, Hyun Jik Kim
Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism...
March 30, 2018: Applied Microbiology and Biotechnology
Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire, Malika Ait-Goughoulte, Stéphane Daffis, Simon P Fletcher, Anna Salvetti, François-Loïc Cosset, Fabien Zoulim, David Durantel
Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters...
March 29, 2018: Scientific Reports
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