The devastating effects of viral diseases such as COVID-19, AIDS, smallpox, polio, influenza, diarrhea, and hepatitis are well known, and studies of viral pathogens are easily justified from a world health perspective.  The need for well-trained and imaginative virologists in the public health community is clear. During the next 25 years, the world population will increase by 2.5 billion people (mostly in developing countries), and increasing global trade, changes in insect vector populations, global climate change, pressure on agricultural resources, and possible bioterrorism all demand that the U.S. view viral diseases from a world health perspective. In spite of significant advances in the development of vaccines and antiviral agents, the death toll from viral diseases continues to climb.  Many sobering examples of emerging viral diseases have occurred since our Virology Training Program was initiated in 2002. Among these are the sudden emergence of the coronavirus that causes severe acute respiratory syndrome (SARS), the continued transmission of an avian influenza virus to humans (“bird flu”), and the isolation of poliovirus vaccine-wild type recombinants that have hampered poliovirus eradication efforts.  More recently, the emerging Middle East Respiratory Syndrome (MERS) coronavirus, and new influenza serotype H7N9, are causing alarm among health care experts worldwide, and the threat of another Ebola virus outbreak following the recent 2014 outbreak in Africa is cause for concern.  Perhaps the most dramatic illustration in recorded history of the relevance of virology to human health is the ongoing COVID-19 pandemic caused by the SARS-2 coronavirus.  This pandemic rages on and has already taken the lived of several million people around the globe.  In addition, the threat of bioterrorism became a reality on U.S. soil with the release of Bacillus anthracis, creating an obligation for scientists to respond with aggressive countermeasures. The importance of viruses, however, extends far beyond their disease-causing potential. When properly harnessed, viruses can be powerful research tools for dissecting cellular processes, and also offer great promise as expression and delivery systems for vaccines and therapeutic agents. 

 

In recognition of the importance of Host-Virus Interactions and Viral Immunology and Vaccine Design in cutting edge virology research, and to optimally leverage the strengths and research interests of Virology Program members, the Program made the decision this past year to focus its training grant on these two fundamentally significant areas of research.  Host-Virus Interactions broadly encompasses several rapidly growing areas, including but not limited to: virus-cell interactions, antiviral innate immunity, and immune evasion by viruses. As obligate parasites with constrained coding capacity, viruses have evolved to hijack cellular host factors and machineries to facilitate their replication.  The study of interactions between viral and host proteins continues to play an enormously important role in elucidating fundamental tenets of molecular and cell biology, including gene expression and regulation, RNA biology, intercellular communication, and protein and membrane trafficking.  While, as mentioned above, viruses masterfully usurp host cell machinery to facilitate their productive replication, cells are not passive vessels for virus propagation.  Cells have evolved robust defenses against invading viral pathogens.  The study of these defense mechanisms offers fresh insights into both the virus and the host cell. Viruses have evolved a variety of strategies to evade innate and adaptive immunity. These outcomes of evasions lower the immune threshold to infections and allows for virus replication, spread, and ensuing diseases. The studies of these mechanisms will help in the understanding of viral pathogenesis resulting in the means to prevent infections.  Presently, the World Health Organization (WHO) is involved in the development and/or implementation of viral vaccine programs for: acute respiratory viruses (including Respiratory syncytial virus, Parainfluenza virus, and SARS-2), Dengue virus, Japanese encephalitis virus, Yellow fever virus, Hepatitis A, B, and C viruses, Human immunodeficiency virus, Measles virus, Mumps virus, Poliovirus, Rotavirus, Human papilloma virus, and Chicken pox virus. Many vaccine strategies rely on the attenuation of viruses to produce “live” vaccines. Knowledge of viral replication is also essential to understanding the molecular basis for attenuation because genetic lesions in attenuated viruses are often located in replicase proteins or in non-coding regions of the genome.

 

These and related areas of Host-Virus interactions dovetail with the adaptive immune response to invading viral agents, which in turn informs the development of vaccines to combat viral infection. The most successful approach to combatting viral infection is the development of effective vaccines that induce both mucosal and systemic immune responses to cope with infection and viral spread. Our Program focuses on several important viral diseases to develop novel strategies by engineering viral antigens to produce the broad neutralizing antibody and T cell immune responses against HIV, influenza, and dengue viruses. Since most viruses initiate their infections through mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts, delivery of vaccine antigens through the mucosal surface would be an ideal route to achieve mucosal, and potentially, systemic immunity. Program mentors are also engaged in research aimed at developing effective mucosal vaccine delivery platforms for HIV, influenza, respiratory syncytial virus, SARS-2, and herpesvirus.

 

By bringing together human, animal, and plant virologists in an integrative program that broadens the research perspectives and abilities of new virologists, the Virology Program at the University of Maryland is training students to make connections across the broad field of virology. The new emphasis on Virus-Host Interactions and Viral Immunology and Vaccine Design sharpens the focus on what we consider to be two key aspects of modern virology research.  The proximity of world-class virus research programs at the University of Maryland (College Park), the Virginia-Maryland Regional College of Veterinary Medicine (College Park), the National Institutes of Health (Bethesda and Frederick) makes this unique training opportunity possible.  Indeed, the breadth of institutions and mentor expertise in this Virology Program is arguably unparalleled anywhere in the U.S.

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The University of Maryland Virology Program thus represents a truly unique environment for students with an interest in virology.  Students who train in our program get a first-hand look at laboratories and investigators across a range of academic and government institutions, providing a wide horizon that is critical for today’s challenging job market.  Graduate training in virology also prepares scientists for research in many related disciplines.  Virology has become a complex field moving far beyond “classical” virology to include large areas of molecular biology, structural biology, biochemistry, cell biology, epidemiology, genomics, and vaccine research. The main emphasis of our training program on virus-host interactions and viral immunology/vaccine design will educate trainees in these multiple disciplines as they progress toward becoming independent scientists. We are committed to continue offering these opportunities to highly motivated students, with a special outreach to minority students, who will greatly enrich the potential of our program to impact global public health.