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Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome.

Frontiers in immunology | 2016

Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.

Pubmed ID: 28096800 RIS Download

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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1000 Genomes: A Deep Catalog of Human Genetic Variation (tool)

RRID:SCR_006828

International collaboration producing an extensive public catalog of human genetic variation, including SNPs and structural variants, and their haplotype contexts, in an effort to provide a foundation for investigating the relationship between genotype and phenotype. The genomes of about 2500 unidentified people from about 25 populations around the world were sequenced using next-generation sequencing technologies. Redundant sequencing on various platforms and by different groups of scientists of the same samples can be compared. The results of the study are freely and publicly accessible to researchers worldwide. The consortium identified the following populations whose DNA will be sequenced: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States. The goal Project is to find most genetic variants that have frequencies of at least 1% in the populations studied. Sequencing is still too expensive to deeply sequence the many samples being studied for this project. However, any particular region of the genome generally contains a limited number of haplotypes. Data can be combined across many samples to allow efficient detection of most of the variants in a region. The Project currently plans to sequence each sample to about 4X coverage; at this depth sequencing cannot provide the complete genotype of each sample, but should allow the detection of most variants with frequencies as low as 1%. Combining the data from 2500 samples should allow highly accurate estimation (imputation) of the variants and genotypes for each sample that were not seen directly by the light sequencing. All samples from the 1000 genomes are available as lymphoblastoid cell lines (LCLs) and LCL derived DNA from the Coriell Cell Repository as part of the NHGRI Catalog. The sequence and alignment data generated by the 1000genomes project is made available as quickly as possible via their mirrored ftp sites. ftp://ftp.1000genomes.ebi.ac.uk ftp://ftp-trace.ncbi.nlm.nih.gov/1000genomes

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Bio-Rad Laboratories (tool)

RRID:SCR_008426

Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.

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Quantity One 1-D Analysis Software (tool)

RRID:SCR_014280

Software used for Bio-Rad imaging systems to acquire, quantitate, and analyze a variety of data. The software allows automatic configuration of imaging systems with appropriate filters, lasers, LEDs, and other illumination sources. It also contains tools for automated analysis of tests and assays such as 1-D electrophoretic gels, western blots, and colony counts.

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HUVEC-C (tool)

RRID:CVCL_2959

Cell line HUVEC-C is a Finite cell line with a species of origin Homo sapiens

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IFITM2/3 antibody (antibody)

RRID:AB_11182821

This monoclonal targets IFITM2/3

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IFITM1-Specific antibody (antibody)

RRID:AB_2233405

This monoclonal targets IFITM1-Specific

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Vero C1008 (cell line)

RRID:CVCL_0574

Cell line Vero C1008 is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus

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A-549 (cell line)

RRID:CVCL_0023

Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

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IFITM1-Specific antibody (antibody)

RRID:AB_2233405

This monoclonal targets IFITM1-Specific

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IFITM2/3 antibody (antibody)

RRID:AB_11182821

This monoclonal targets IFITM2/3

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A-549 (cell line)

RRID:CVCL_0023

Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

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Vero C1008 (cell line)

RRID:CVCL_0574

Cell line Vero C1008 is a Spontaneously immortalized cell line with a species of origin Chlorocebus sabaeus

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