Marli Azevedo, M.S., Ph.D.
Division of Microbiology
National Center for Toxicological Research (NCTR)
Ph.D. - Virus Immunology, The Ohio State University, USA
Post-doctoral fellow - Virus Immunology, The Ohio State University, USA
Academic Positions - Research Scientist and Adjunct Assistant Professor, The Ohio State University
FDA Experience - 4 years
Our current studies are focused on respiratory and enteric viruses, among them: Coronaviruses and Noroviruses. Coronaviruses are responsible for causing acute respiratory tract infections in humans and respiratory, gastrointestinal, neuropathies and systemic diseases in animals. Noroviruses are responsible for 60% of the food and waterborne gastroenteritis outbreaks. Twenty-three million Americans are sickened with Norovirus yearly, accounting for 50,000 hospitalizations and 300 deaths.
We have used qRT-PCR, RT-PCR, plaque assay, virus isolation, cloning, sequencing, confocal microscopy, immunofluorescence assay and cell culture, among other techniques, to study the mechanism of transmission of coronavirus and to determine the current strains circulating in humans and animals in Arkansas. We have identified a feline and a canine norovirus circulating in Arkansas. We have also constructed a norovirus-like particle to assess the exposure to canine or feline norovirus by humans. We are currently exploring a cell culture model to support norovirus replication.
Proposed Research Project for an FDA Commissioner's Fellow
Influenza virus infects 5-15% of the world population causing approximately 500,000 deaths annually. During Influenza pandemics, especially those caused by H1N1 strains, up to 20% of the influenza infected individuals develop bacterial pneumonia.
Secondary bacterial pneumonia is the most frequent type of pneumonia seen during an influenza epidemic. The most prevalent ethological agents of these respiratory secondary bacterial infections are Streptococcus pneumoniae and Staphylococcus aureus. The occurrence of S. aureus antibiotic resistance is always a primary concern, particularly if the organism is hospital-acquired. Worldwide, greater than 95% of patients with a S. aureus infection do not respond to first-line antibiotics like penicillin or ampicillin and the number of methicillin resistant S. aureus (MRSA) continues to rise with the organism being endemic in many hospitals. MRSA have an intrinsic resistance to all ß-lactam antibiotics and tend to acquire multiple other unrelated resistance determinants as well. In the case of these multiple-drug resistant S. aureus, vancomycin has historically been the drug of choice. However, intermediate resistance to vancomycin has been reported both abroad and in the United States. Recently clinical strains of S. aureus carrying the vanA gene and exhibiting resistance to vancomycin at high levels have been isolated.
Exacerbation of influenza infection by secondary bacterial infections has been demonstrated in inbred and outbred mice, monkeys and documented in humans. Influenza virus induced Interferon Type I and II, IL-10 and suppression of Th17 cytokines have been associated with the exacerbation of secondary bacterial infections.
However, differing outcomes have been reported, which seem to be linked to studies using different influenza strains. Based on these observations the FDA fellow will explore the potential of different strains of influenza virus to induce bacterial pneumonia. Mice will be co-infected or super-infected with Influenza virus and S. aureus. The animals will be evaluated for clinical signs of pneumonia, pathologies and characterization of cellular and humoral immune responses. The FDA fellow will explore if the presence of influenza recombinant proteins could also affect respiratory bacterial infection as ways.
This project will provide the basis to understand the mechanism by which influenza virus contributes to bacterial pneumonia. It also has the potential to predict an increase in the number of cases of bacterial pneumonia according to the circulating influenza strain. This project will help to determine possible targets for therapy development and prevention of post-influenza bacterial pneumonia.
Pneumonia is a leading cause of death worldwide and the 9th cause of death annually in the US. Both influenza virus and S aureus alone are two major threats to public health. Understanding the triggers to secondary bacterial infection by Influenza virus will contribute to the FDA preparedness to evaluate the development of new technology for diagnostic, treatment and prevention. This is a critically important area as novel strains of influenza can quickly emerge and their role in inducing secondary pneumonia should be rapidly evaluated. The intra-center collaboration with Dr. Mark Hart is essential to the success of the project, through his S. aureus’ expertise (Iverson et al., J. Infect. Dis., 203:880–888, 2011. Inter-center collaboration will leverage resources and expertise that will help ensure the accomplishment of our aim. The outcomes of this project will also support the regulatory mission of other centers such as CDER and CDRH by providing the bases for approval of diagnostic and prevention of influenza induced secondary bacterial infection.
The FDA Regulatory Science Priority Area for the project is Facilitate Development of Medical Countermeasures to Protect Against Threats to US and Global Health and Security.
Applicants are expected to have previous experience with enteric or respiratory viruses and bacterial pathogens, knowledge of molecular biology, immunology, tissue culture, flow cytometry and small animal model. The ideal candidate will have a Ph.D. Biochemistry, Molecular Biology, immunology or virology.
Selected Recent Publications
- Jee J, Hoet AE, Azevedo MP, Vlasova A, Loerch SC, Pickworth CL, Hanson J, Saif LJ. 2013. Effects of dietary vitamin A content on antibody responses of feedlot calves inoculated intramuscularly with an inactivated bovine coronavirus vaccine. Am J Vet Res. 74(10):1353-62
Azevedo MP, Vlasova AN, Saif LJ. 2013. Human rotavirus virus-like particle vaccines evaluated in a neonatal gnotobiotic pig model of human rotavirus disease. Expert Rev. Vaccines 12(2):169-181.
- Azevedo MSP, Zhang W, Wen K, Gonzalez A M, Saif LJ, Yousef AE and Yuan L. 2012. Lactobacillus acidophilus and L. reuteri modulate cytokine responses in gnotobiotic pigs infected with human rotavirus. Beneficial Microbes 3(1):33-42.
- Mullis LB, Saif LJ, Zhang Y, Zhang X and Azevedo MSP. 2012. Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions. Food Microbiology 30(1):180-6.
Wen K, Li G, Zhang/W, Azevedo MSP, Saif LJ, Liu F, Bui T, Yousef A and Yuan L. 2011. Development of -T cell subset responses in gnotobiotic pigs infected with human rotaviruses and colonized with probiotic lactobacilli. Vet. Immunol. Immunopathol. 141(3-4):267-75.
- Wang Y, Azevedo M, Saif LJ, Gentsch JR, Glass RI, Jiang B. 2010. Inactivated rotavirus vaccine induces protective immunity in gnotobiotic piglets. Vaccine. 28(33):5432-6.