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Archive - Apr 17, 2020

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Individual Genetic Variation in Immune System Genes (HLA) May Affect Differences in Severity of COVID-19 Infection and Susceptibility

Genetic variability in the human immune system may affect susceptibility to, and severity of infection by, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19). The research was published online on April 17, 2020 in the Journal of Virology, a publication of the American Society for Microbiology. The open-access article is titled “Human Leukocyte Antigen Susceptibility Map for SARS-CoV-2.” Individual genetic variation may explain differences in the strength of immune responses. Certain immune system genes, called human leukocyte antigen (HLA) genes that are involved in recognizing pathogens, vary from person to person. Variations can influence how well the immune system recognizes a given pathogen. Poor recognition of SARS-CoV-2 could cause a person to be more vulnerable to the virus. "In particular, understanding how variation in HLA [a component of the immune system containing multiple genes] may affect the course of COVID-19 could help identify individuals at higher risk from the disease," according to the authors of the new study, who are from Oregon Health & Science University, Portland, Oregon, and the Portland VA Research Foundation. The first author is PhD candidate Austin Nguyen, and the senior author is Reid F. Thompson, MD, PhD, both from the Oregon Health & Science University. The authors show that individual HLA, haplotype, and full genotype variability likely influence the capacity to respond to SARS-CoV-2 infection, and note that certain alleles in particular could be associated with more severe infection, as has previously been shown with SARS-CoV (the SARS virus).

Researchers Move Closer to Producing Heparin Anti-Coagulant in the Lab; UC San Diego Group Demonstrates Influence of Transcription Factor ZNF263 on Heparin Synthesis

In a recent study published online on April 10, 2020in the Proceedings of the National Academy of Sciences (PNAS), University of California (UC) San Diego researchers moved one step closer to the ability to make heparin (image) of structure) in cultured cells. The article is titled “ZNF263 Is a Transcriptional Regulator of Heparin and Heparan Sulfate Biosynthesis.” Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible. In particular, the researchers found a critical gene in heparin biosynthesis: ZNF263 (zinc-finger protein 263). The researchers believe this gene regulator is a key discovery on the way to industrial heparin production. The idea would be to control this regulator in industrial cell lines using genetic engineering, paving the way for safe industrial production of heparin in well-controlled cell culture. Heparin is currently produced by extracting the drug from pig intestines, which is a concern for safety, sustainability, and security reasons. Millions of pigs are needed each year to meet our needs, and most manufacturing is done outside the USA. Furthermore, ten years ago, contaminants from the pig preparations led to dozens of deaths. Thus, there is a need to develop sustainable recombinant production. The work in PNAS provides new insights on exactly how cells control synthesis of heparin. Heparin is a special subtype of a more general class of carbohydrates, called heparan sulfates, that are produced by a wide range of cells, both in the human body, as well as in cell culture. Yet, heparin is exclusively produced in a special type of blood cells called mast cells. To this day, heparin cannot be successfully produced in cell culture.

New Ebola Vaccine May Fight All Four Ebola Virus Species That Infect Humans

Infectious disease scientists report early development of a potential universal vaccine for Ebola viruses that preclinical tests show might neutralize all four species of these deadly viruses infecting people in recent outbreaks, mainly in Africa. Scientists at Cincinnati Children's Hospital Medical Center report their preclinical results in an article published online on February 19, 2020 in the Journal of Virology, published by the American Society for Microbiology. The article is titled “A Bivalent, Spherical Virus-Like Particle Vaccine Enhances Breadth of Immune Responses Against Pathogenic Ebola Viruses in Rhesus Macaques.” Although still in early preclinical testing, the researchers report that their data indicate that the prospective vaccine has potential to be a stand-alone protection from Ebola. It also could broaden and extend the durability of protective immunity induced by current live vaccines already being tested in clinical trials against individual Ebola virus species, said Karnail Singh, PhD, the study's co-principal investigator in the Division of Infectious Diseases at Cincinnati Children’s. "This could be a significant advancement in the global effort to prevent or manage Ebola outbreaks, especially if this vaccine, used alone or in combination with another Ebola vaccine, results in long-term and durable protective immunity against different Ebola viruses," Dr. Singh said. A deadly Ebola outbreak in West Africa between 2013 and 2016 accelerated international efforts to develop vaccines for these highly infectious and harmful viruses. This led to development of recombinant Ebola vaccines in which glycoprotein from Zaire Ebola virus is engineered into another modified live viral vector.