Herbert W. "Skip" Virgin | |
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Herbert W. "Skip" Virgin was the Edward Mallinckrodt Professor and Chair of the Department of Pathology & Immunology at the Washington University School of Medicine [1] and a member of the National Academy of Sciences. [2] He is best known for establishing murine norovirus as a model system for studying norovirus biology, for identifying host phenotypes associated with persistent viral infections, for defining alterations to the human virome in the context of different diseases, and for elucidating the roles of autophagy and interferon-stimulated genes during viral infection.
Herbert Virgin was born in Miami, Florida and studied biology at Harvard University as an undergraduate, graduating magna cum laude. He obtained his M.D. and Ph.D. from Harvard Medical School, with his thesis work focusing on host immune responses to Listeria monocytogenes , and completed his residency in internal medicine at Brigham and Women's Hospital. [3] Following post-doctoral training in the laboratory of Bernard Fields, he joined the faculty of the Washington University School of Medicine. He remained at Washington University until 2018, most recently as Chair of the Department of Pathology & Immunology. Virgin left St. Louis to enter the biomedical industrial sector, and was succeeded as chairman by Richard J. Cote.
Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the IFNG gene.
Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.
The type III interferon group is a group of anti-viral cytokines, that consists of four IFN-λ (lambda) molecules called IFN-λ1, IFN-λ2, IFN-λ3, and IFN-λ4. They were discovered in 2003. Their function is similar to that of type I interferons, but is less intense and serves mostly as a first-line defense against viruses in the epithelium.
Signal transducer and activator of transcription 4 (STAT4) is a transcription factor belonging to the STAT protein family, composed of STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6. STAT proteins are key activators of gene transcription which bind to DNA in response to cytokine gradient. STAT proteins are a common part of Janus kinase (JAK)- signalling pathways, activated by cytokines.STAT4 is required for the development of Th1 cells from naive CD4+ T cells and IFN-γ production in response to IL-12. There are two known STAT4 transcripts, STAT4α and STAT4β, differing in the levels of interferon-gamma production downstream.
Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). STAT2 sequence identity between mouse and human is only 68%.
Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ISG15 gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response.
Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.
Ubiquitin specific peptidase 18 (USP18), also known as UBP43, is a type I interferon receptor repressor and an isopeptidase. In humans, it is encoded by the USP18 gene. USP18 is induced by the immune response to type I and III interferons, and serves as a negative regulator of type I interferon, but not type III interferon. Loss of USP18 results in increased responsiveness to type I interferons and life-threatening autoinflammatory disease in humans due to the negative regulatory function of USP18 in interferon signal transduction. Independent of this activity, USP18 is also a member of the deubiquitinating protease family of enzymes. It is known to remove ISG15 conjugates from a broad range of protein substrates, a process known as deISGylation.
Interferon-induced GTP-binding protein Mx2 is a protein that in humans is encoded by the MX2 gene.
CMRF35-like molecule 1, also known as CD300lf, is a protein that in humans is encoded by the CD300LF gene. CD300lf belongs to the protein family of CD300. CD300lf is a membrane glycoprotein that contains an immunoglobulin domain and is expressed by myeloid and mast cells of humans and other mammals. The protein functions in immunoregulation but might also have a role in norovirus infections.
In molecular biology, the guanylate-binding proteins family is a family of GTPases that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups: the small 47-KD immunity-related GTPases (IRGs), the Mx proteins, and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class.
Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.
Murine norovirus (MNV) is a species of norovirus affecting mice. It was first identified in 2003. MNV is commonly used in research to model Human norovirus because the latter is difficult to grow in the laboratory. Standardized cell cultures are used in MNV propagation and the virus naturally infects mice, which allows studies in animal systems.
Akiko Iwasaki is a Sterling Professor of Immunobiology and Molecular, Cellular and Developmental Biology at Yale University. She is also a principal investigator at the Howard Hughes Medical Institute. Her research interests include innate immunity, autophagy, inflammasomes, sexually transmitted infections, herpes simplex virus, human papillomavirus, respiratory virus infections, influenza infection, T cell immunity, commensal bacteria, COVID-19 and Long COVID.
Interferon lambda 4 is one of the most recently discovered human genes and the newest addition to the interferon lambda protein family. This gene encodes the IFNL4 protein, which is involved in immune response to viral infection.
Francis "Frank" Vincent Chisari is a physician, experimental pathologist, virologist, and immunologist, known for his research on virus-host interactions of hepatitis B and hepatitis C.
De’Broski. R. Herbert is an immunologist, parasitologist, academic, and biomedical researcher. He is currently Full Professor of Immunology, and Penn Presidential Professor at the University of Pennsylvania School of Veterinary Medicine. He is also the Associate Director for Institute of Infectious and Zoonotic Disease (PennVet), and an affiliated Scientist at the Monell Chemical Senses Center.
Aaron Frederick "Fred" Rasmussen Jr. was an American physician, professor of microbiology and immunology, and, later in his career, associate dean of the UCLA School of Medicine. He is known for his pioneering research in psychoneuroimmunology.
Edwin Herman Lennette was an American physician, virologist, and pioneer of diagnostic virology.