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Pathogens
Astroviruses
CII researchers have identified a novel mink-related astrovirus in the brain of a patient afflicted with unexplained encephalitis. Astroviruses are traditionally found as the cause of non-lethal gastroenteritis in children and adults. This discovery is among the first implicating an astrovirus in inflammation of the brain. CII researchers are continuing to work on the genomic sequence as well as the production of its capsid protein.
Enteroviruses Globally, enteroviruses infect millions of people each year. There are over 70 enteroviruses and many are associated with asymptomatic infection. These viruses do, however, cause a variety of illnesses and diseases, including mild respiratory illness; hand, foot, and mouth disease; acute hemorrhagic conjunctivitis; aseptic meningitis; myocarditis; and severe neonatal sepsis-like disease. Annually in the United States, enteroviruses infect between thirty and fifty million people, causing between 30,000 and 50,000 hospitalizations for meningitis. Improved general hygiene and sanitation are classic and effective prevention measures, but no specific antiviral therapy is available for treatment. Surveillance and reporting of enteroviruses are also important practices for containing the occasional outbreaks that these viruses can cause. One of the most recent of these outbreaks was a hand, foot and mouth disease outbreak due to enterovirus 71 (EV71) in Fuyang City, Anhui Province.
CII researchers have applied microarray technology to the serotyping of enteroviruses, a large genus of viruses whose most famous member is the poliovirus. Serotyping of enteroviruses allows public health professionals and health care providers to treat the disease with more specificity and also to impact vaccine prioritization. Lacking mobile and inexpensive diagnostic tools, health practitioners are most often unable to attribute illness to a specific pathogenic enterovirus serotype. Thus far, microarrays for enteroviruses made from reference strains and clinical isolates have been validated. The next and ultimate step in this project is to validate the technology for clinical samples, which poses a challenge as the samples have a lower viral titer than clinical isolates expanded in the laboratory. Regardless, this work is the foundation for practical diagnostic and surveillance technology that will help to treat patients and prevent the spread of disease.
Rhinoviruses
Acute respiratory infection is a significant cause of morbidity and mortality in children worldwide. Globally, rhinoviruses cause up to half of all acute respiratory tract infections, also known as the common cold. After discovering a novel rhinovirus, CII scientists worked with samples from hospitalized children suffering from severe respiratory tract infections in Germany. Despite the application of PCR assays as well as clinical diagnostic methods, it is commonly impossible to implicate and agent in up to 50% of cases of severe respiratory disease. Through this study, CII was able to determine that a novel rhinovirus was the cause in several unexplained pediatric respiratory infections. CII investigators are currently setting up another international, multi-center study with medical centers in the Gambia and South Africa, in order to discover the causes of respiratory illness in children. Using the state-of-the-art molecular assays it has pioneered, CII hypothesizes that both novel and familiar rhinoviruses will be implicated.
West Nile Virus
In 1999 CII scientists, then at the University of California, in association with colleagues at the Wadsworth Center, New York State Department of Health, investigated an outbreak of what was thought to be due to St. Louis encephalitis virus, using novel molecular methods. They found instead that the cause was a new strain of West Nile virus, never before seen in the Western hemisphere. After issuing this initial report, they sequenced the entire genome of the virus and developed sensitive tests for surveillance and diagnosis that were invaluable as this virus spread across North America.
Bunyavirus
Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, California encephalitis virus, Sin Nombre virus and hantaviruses are members of the Bunyavirus family. Because of the morbidity and mortality that Bunyaviruses can cause, many are classified as Category A and B priority pathogens by NIAID. These segmented viruses can cause severe hemorrhagic fever and encephalitis, as well as adult respiratory disease, and are widely distributed geographically. Mosquitoes, ticks, and sandflies, including these animals’ bodily excretions, spread these viruses.
Viruses with segmented genomes have the capacity to expand their genetic diversity not only through slow genetic drift – a result of the accumulation of individual point mutations - but also through sudden genetic shift. Sudden genetic shift may result from a new arrangement of whole genome segments in the progeny viruses that are produced during a coinfection event. CII researchers are investigating members of this viral family and the drastically different viruses they exhibit due to their high propensity for reassortment occurring in even just one replication round.
CII scientists have published papers on Ngari virus and Guaroa virus. With Ngari virus, CII researchers are investigating the source of new segments of genetic material that have been incorporated into this recently recognized reassortant. After suggesting Batai virus as a donor of some segment sequences to Ngari virus, CII analyzed samples from mosquitos in Uganda and from patients in Sudan with febrile illness; results suggest a role of the Ngari reassortant virus in severe human illness throughout East Africa. With Guaroa virus, CII has used cross-reactivity to link the segmented virus to the Bunyamwera serogroup.
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