Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Most people infected with Zika virus don’t get sick. This is the same family to which dengue virus, yellow fever virus, and West Nile virus belong. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. “The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment, used to create an effective vaccine or to improve our ability to diagnose and distinguish Zika infection from that of other related viruses,” Kuhn says. PMID: 27033547. The structure of the so-called “mature virus” bears resemblance to a golf ball in that the major surface protein E lies parallel to the viral membrane, thus presenting a rather smooth surface (Figure 2A and B)… Zika virus (ZIKV) has emerged as major health concern, as ZIKV infection has been shown to be associated with microcephaly, severe neurological disease and possibly male sterility. Protein crystallography studies performed at the ALS have now resolved the structure of a key ZIKV protein (NS5) to 3.0 Å. The structure differs from the mature Zika virus in that the membrane protein in the mature virus is covered by the envelope protein. Microcephaly is a condition marked by an unusually small head, brain damage, and developmental delays. Bldg. |   Get the latest research information from NIH. References: The 3.8 Å resolution cryo-EM structure of Zika virus. Email. Courtesy of Kuhn and Rossmann research groups, Purdue University, the latest public health information from CDC, Autoimmune Lymphoproliferative Syndrome (ALPS), Characterizing Food Allergy & Addressing Related Disorders, Prevention, Treatment & Control Strategies, Strategic Partnerships & Research Capacity, Primary Immune Deficiency Diseases (PIDDs), Partnership for Access to Clinical Trials (PACT), Division of Allergy, Immunology, and Transplantation, Division of Microbiology and Infectious Diseases, Dr. Joseph Kinyoun The Indispensable Forgotten Man, Dr. Joseph Kinyoun: Selected Bibliography, Clinical Trial in Hospitalized COVID-19 Patients Evaluates Long-Acting Antibody Therapy, Intranasal Influenza Vaccine Spurs Strong Immune Response in Phase 1 Study, Scientists Identify Locations of Early Prion Protein Deposition in Retina, The 3.8Å resolution cryo-EM structure of Zika virus, Investigational mRNA Vaccine Protects Mice and Monkeys from Zika Virus Infection, Immune Molecule Protects Against Zika Virus Infection in Animal Models, Zika Infection Damages Mouse Testes, NIAID-Supported Study Finds, Zika Virus Spread Undetected for Many Months, NIH-Supported Study Finds, Zika Virus Infection May Be Prolonged in Pregnancy, Natural Lipid Acts as Potent Anti-Inflammatory, Theodore Pierson, Ph.D., of NIAID’s Laboratory of Viral Diseases, a co-author on the paper, Cristina Cassetti, Ph.D., of NIAID’s Division of Microbiology and Infectious Diseases. Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, Kuhn RJ. Learn about the basic biology, origins, life cycle, and symptoms of Zika virus. The mosquito vectors typically breed in domestic water-holding containers; they are aggressive daytime biters and feed both indoors and outdoors near dwellings. The incredible image above is the 3D structure of the Zika virus, which has only just been revealed. Animal & human viruses. The structure might also point to new approaches for vaccine development or improved diagnostics for Zika infection, the researchers say. Zika virus is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. ARTICLE: Prasad VM(1), Miller AS(1), Klose T(1), Sirohi D(1), Buda G(1), Jiang W(1), Kuhn RJ(1), Rossmann MG(1). The team included NIAID investigator Theodore Pierson, Ph.D. The process involves freezing virus particles and firing a stream of high-energy electrons through the sample to create tens of thousands of images. The information may also be useful for designing treatments such as antiviral drugs or antibodies that interfere with E glycoprotein function. A team led by researchers from Tianjin University (P.R. aegypti and Ae. "It illuminates the most promising areas for … COVID-19 is an emerging, rapidly evolving situation. Further, details on the structural differences between E glycoprotein of Zika virus and the same protein in dengue virus may make it possible to create diagnostic tests that can distinguish Zika virus infection from dengue infection, a critical need in countries where both Zika and dengue viruses are circulating. In 2013, the virus caused an outbreak in French Polynesia. NIH Research Matters Kuhn and Rossmann research groups, Purdue University, U.S. Department of Health & Human Services, NIH Institute and Center Contact Information, Get the latest public health information from CDC », Get the latest research information from NIH », NIH staff guidance on coronavirus (NIH Only) », Video: Zika Virus: A Pandemic in Progress, Block the Buzzing, Bites, and Bumps: Preventing Mosquito-Borne Illnesses. Since that time, the virus has spread to other countries and territories in Central and South America as well as the Caribbean, including Puerto Rico and the U.S. Virgin Islands. The biology of Zika virus. Symptoms can include fever, rash, joint pain, and conjunctivitis (pink eye). The variation in the Zika envelope (E) glycoproteins—180 of which are packed on the virus’s outer shell—may provide clues to better understand how Zika virus enters human cells and suggests ways to combat the virus with drugs or vaccines aimed at the newly detailed region. The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Zika virus is transmitted to humans primarily through the bite of an infected Aedes species mosquito (Ae. Symptoms are generally The structure differs from the mature Zika virus in that the membrane protein in the mature virus is covered by the envelope protein. The majority of people infected with Zika virus do not develop symptoms. WHAT: A near-atomic level map of Zika virus shows its structure to be largely similar to that of dengue virus and other flaviviruses, but with a notable difference in one key surface protein, report scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The work was funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The structure provides clues to understanding how Zika virus enters human cells and suggests ways to design drugs or vaccines to combat the virus. News Releases. Prior studies had established the structures of several of the DENV serotypes [3–7], WNV [8], and most recently JEV [9]. Jul. Flaviviruses may use this glycoprotein region to attach to and enter human cells. As the largest protein component within the ZIKV replication complex, NS5 plays key roles in the life cycle and surviva … These 2-D images are then combined to yield a detailed 3-D view of the virus. National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, U.S. Department of Health and Human Services. The incubation period (the time from exposure to symptoms) of Zika virus disease is estimated to be 3–14 days. “The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment,” says study co-author Dr. Richard Kuhn of Purdue University. D Sirohi et al. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. Office of Communications and Public Liaison. Zika virus antibody testing is also complicated by cross-reactivity with other flaviviruses, which may make conclusive determination of which flavivirus is responsible for the person’s recent infection difficult. Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor. Bethesda, MD 20892-2094, Lasting immunity found after recovery from COVID-19, Final report confirms remdesivir benefits for COVID-19, Experimental coronavirus vaccine highly effective, Hydroxychloroquine doesn’t benefit hospitalized COVID-19 patients, Immune cells for common cold may recognize SARS-CoV-2. Intro to viruses. If the site on the envelope glycoprotein functions in Zika as it does in related viruses, the detailed structure might help scientists design ways to block viral attachment and entry to human cells. WHAT: The structure reveals that Zika virus is similar to other flaviviruses, such as Dengue virus and West Nile virus. Similar to other flavivirus proteases, such as those of dengue virus (DENV) and West Nile virus (WNV), the mature form of ZIKV protease consists … 5B52, MSC 2094 Structure of the immature Zika virus at 9 Å resolution. The biology of Zika virus. Cryo-EM structure of immature Zika virus. The following individuals are available to comment on the research: NOTE: Contact Elizabeth Gardner, Purdue University, at ekgardner@purdue.edu or (765) 494-2081 for audiovisual content about this research and to request interviews with Purdue University researchers Richard Kuhn and Michael Rossmann. A representation of the surface of the Zika virus with protruding envelope glycoproteins (red) shown. The Zika virus surface is similar to that of dengue and related viruses at the near-atomic level, researchers found, but with a notable difference. The structure of Zika virus is similar to other known flavivirus structures except for the ~10 amino acids that surround the Asn154 glycosylation site found in each of the 180 envelope glycoproteins that … Other flaviviruses include dengue, yellow fever, and West Nile viruses. 2016 Mar 31. pii: aaf5316. Findings also show differences between the immature Zika virus and immature versions of other flaviviruses. Results appeared online on March 31, 2016, in Science. A near-atomic level map of Zika virus shows its structure to be largely similar to that of dengue virus and other flaviviruses, but with a notable difference in one key surface protein. The Zika virus, like influenza and HIV, captures cell membrane material from its host during the replication process. He noted that one of the most challenging aspects is extracting virus particles of sufficient quality to analyze. 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