Microbiologist — Division of Microbiology
Marli Azevedo, Ph.D.
Dr. Marli Azevedo studied pharmacy and clinical biochemistry at the Federal University of Goias, Brazil. She attended the Institute of Tropical Pathology in Brazil, where she earned a Master of Science in tropical medicine with a focus in virology studying diarrheal diseases affecting HIV patients. She earned a Ph.D. in virus immunology at The Ohio State University in 2005, focusing on vaccine design and enteric virus pathogenesis. From 2005 to 2007, she trained at The Ohio State University as a postdoctoral fellow. In 2007, she attained an academic position as a research scientist and adjunct assistant professor at Food Animal Health Research Program at The Ohio State University. In 2009, she joined the Division of Microbiology at NCTR.
Before joining FDA, Dr. Azevedo dedicated 10 years studying rotavirus immunity. Using gnotobiotic pigs, because of their similarity to human babies, Dr. Azevedo demonstrated viremia and virus infection in the respiratory tract of gnotobiotic piglets after infection with rotavirus. In addition, Dr. Azevedo has studied immune responses to rotavirus and identified correlates of protective immunity after rotavirus vaccination. Furthermore, she has tested and evaluated the immunogenicity and protective efficacy of several candidate human rotavirus vaccines and demonstrated the potential to use these vaccines against rotavirus disease in children. Dr. Azevedo has used the Murine norovirus model to better understand norovirus replication, disease pathogenesis, and host responses.
Dr. Azevedo’s 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.
She has 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. She has identified feline and canine norovirus strains circulating in Arkansas. She is currently investigating the role of spike protein of SARS-CoV-2 on immune-mediated pathogenesis and the role of non-structural proteins in COVID-19 morbidity. Dr. Azevedo’s laboratory has also constructed a norovirus-like particle to assess the exposure to canine or feline norovirus by humans, which may also be used to further understand immune responses to norovirus. Her laboratory has also explored models of co-infection of norovirus and Salmonella to study possible models of inference between them, as well as host interactions.
Dr. Azevedo’s laboratory has demonstrated that infection of RAW 264.7 cells with S. enterica reduces the replication of Murine Norovirus Virus (MNV), in part by blocking virus entry early in the virus life cycle and inducing antiviral cytokines later in the infection cycle. In particular, bacterial infection prior to, or during MNV infection affected virus entry, whereas MNV entry remained unaltered when the virus infection preceded bacterial invasion. This block in virus entry resulted in reduced virus replication, with the highest impact on replication observed during conditions of co-infection. In contrast, bacterial replication showed a three-fold increase in MNV-infected cells, despite the presence of antibiotic in the medium. Most importantly, Dr. Azevedo presented evidence that the infection of MNV-infected macrophages by S. enterica blocked MNV-induced apoptosis, despite allowing virus replication. Apoptosis blockade was evidenced by reduction in DNA fragmentation and absence of poly-ADP ribose polymerase, caspase 9, and caspase 3 cleavage events. Suggesting a novel mechanism of pathogenesis whereby initial co-infection with these pathogens could result in prolonged infection by either of these pathogens or both together, by delaying cell death. Her laboratory is currently using knockout cells and bacterial factors to better understand their effect on norovirus replication and on host responses.
Dr. Azevedo’s laboratory also has investigated the effect of silica nanoparticles on norovirus replication and host-cell response during virus infection. Silica nanoparticles did not affect virus load; however, silica nanoparticles reduced the ability of macrophages to up-regulate genes encoding bone morphogenic proteins (BMPs), chemokine ligands, and cytokines for which expression levels were otherwise found to be up-regulated in response to MNV-1 infection. Furthermore, silica nanoparticles present during norovirus infection produced a genotoxic insult to macrophages. Taken together, her study suggests that important safety considerations should be given to reduce exposure to silica nanoparticles in the gastrointestinal tract, especially for individuals infected with noroviruses and possibly other foodborne viruses.
Dr. Azevedo’s lab has cloned and expressed the spike proteins of SARS-CoV-2, HCoV-NL-63 and HCoV-HUK1 in a baculovirus expression system. These proteins have been used to generate polyclonal antibodies that will allow further studies of coronavirus-related disease. Her lab has also generated stable cell lines expressing the non-structural proteins of SARS-CoV-2 and generated cell lines expressing both the CD32A and ACE-2 receptor.
Professional Societies/National and International Groups
American Society for Microbiology
2011 – Present
American Society for Virology
1999 – Present
Brazilian Society for Virology
1991 – Present
Mucosal Immunology Society
2007 – Present
Conformational Changes of the Receptor Binding Domain of SARS-CoV-2 Spike Protein and Prediction of a B-cell Antigenic Epitope Using Structural Data.
Khare S., Azevedo M., and Gokulan K.
Front Artif Intell. 2021, 4:630955. doi: 10.3389/frai.2021.630955. eCollection 2021.
Elucidating Interactions Between SARS-CoV-2 Trimeric Spike Protein and ACE2 Using Homology Modeling and Molecular Dynamics Simulations.
Sakkiah S., Guo W., Pan B., Ji Z., Yavas G., Azevedo M., Hawes J., Patterson T.A., and Hong H.
Front Chem. 2021, 8:622632. doi: 10.3389/fchem.2020.622632. PMID: 33469527; PMCID: PMC7813797.
Genomics Analyses of Novel Canine Norovirus Reveal Species-Specific Clustering of GIV and GVI Norovirus.
Ford-Siltz L.A., Mullis L., Sanad Y.M., Tohma K., Lepore C.J., Azevedo M.P., and Parra G.
Viruses. 2019, 11(3)204:1-16.
Reduced Vancomycin Susceptibility and Increased Macrophage Survival in Staphylococcus aureus Strains Sequentially Isolated from a Bacteraemic Patient During a Short Course of Antibiotic Therapy.
Basco M., Kothari A., McKinzie P., Revollo J., Agnihothram S., Azevedo M., Saccente M., and Hart M.
J. Med. Microbiol. 2019, 68:848-859.
Viral and Bacterial Co-Infection and Its Implications.
Azevedo M., Mullis L., and Agnihothram S.
SF J Virol. 2017, 1(1):1-2.
Titanium Dioxide Nanoparticles Evoke Proinflammatory Response during Murine Norovirus Infection Despite Having Minimal Effects on Virus Replication.
Agnihothram S., Mullis L., Townsend T., Watanabe F., Mustafa T., Biris A., Manjanatha M., and Azevedo M.
International Journal of Nanotechnology in Medicine and Engineering. 2016, 1(3):63-73.
Silicon Dioxide Impedes Antiviral Response and Causes Genotoxic Insult During Calicivirus Replication.
Agnihothram S., Vermudez S., Mullis L., Townsend T., Manjanatha M., and Azevedo M.
J Nanosci Nanotechnol. 2016, 16(7):7720-7730.
Infection of Murine Macrophages by Salmonella enterica Serovar Heidelberg Blocks Murine Norovirus Infectivity and Virus-Induced Apoptosis.
Agnihothram S., Basco M., Mullis L., Foley S., Hart M., Sung K., and Azevedo M.
PLoS One. 2015, 10(12):e0144911.
Human Respiratory Coronaviruses Detected in Patients with Influenza-Like Illness in Arkansas, USA.
Silva C., Mullis L., Pereira O., Saif L., Vlasova A., Zhang X., Owens R., Paulson D., Taylor D., Haynes L., and Azevedo M.
Virology & Micology. 2014, 01(S2):004 1-8
Effects of Dietary Vitamin A Content on Antibody Responses of Feedlot Calves Inoculated Intramuscularly with an Inactivated Bovine Coronavirus Vaccine.
Jee J., Hoet A., Azevedo M., Vlasova A., Loerch S., Pickworth C., Hanson J., and Saif L.
Am J Vet Res. 2013, 74(10):1353-62
Human Rotavirus Virus-Like Particle Vaccines Evaluated in a Neonatal Gnotobiotic Pig Model of Human Rotavirus Disease.
Azevedo M., Vlasova A., and Saif L.
Expert Rev Vaccines. 2013, 12(2):169-181.
Stability of Bovine Coronavirus on Lettuce Surfaces under Household Refrigeration Conditions.
Mullis L., Saif L., Zhang Y., Zhang X., and Azevedo M.
Food Microbiology. 2012, 30(1):180-186.
Lactobacillus Acidophilus and L. Reuteri Modulate Cytokine Responses in Gnotobiotic Pigs Infected with Human Rotavirus.
Azevedo M., Zhang W., Wen K., Gonzalez A., Saif L., Yousef A., and Yuan L.
Beneficial Microbes. 2012, 3(1):33-42.
Development of γδ-T Cell Subset Responses in Gnotobiotic Pigs Infected with Human Rotaviruses and Colonized with Probiotic Lactobacilli.
Wen K., Li G., Zhang W., Azevedo M., Saif L., Liu F., Bui T., Yousef A., and Yuan L.
Vet. Immunol Immunopathol. 2011, 141(3-4):267-275.
Inactivated Rotavirus Vaccine Induces Protective Immunity in Gnotobiotic Piglets.
Wang Y., Azevedo M., Saif L., Gentsch J., Glass R., and Jiang B.
Vaccine. 2010, 28(33):5432-5436.
Innate Immune Responses to Human Rotavirus in Neonatal Gnotobiotic Piglet Disease Model.
González A., Azevedo M., Jung K., Vlasova A., Zhang W., and Saif L.
Immunology. 2010, 131(2):242-256.
Oral Versus Intranasal Prime/Boost Regimen Using Attenuated HRV or 2/6VLP with ISCOM Influences Protection and Antibody Secreting Cell Responses to Rotavirus in a Neonatal Gnotobiotic Pig Model.
Azevedo M., Gonzalez A., Yuan L., Jeong K., Iosef C., Nguyen T., Lovgren-Bengtsson K., Morein B., and Saif L.
Clin Vaccine Immunol. 2010, 17(3):420-8.
Toll-Like Receptor and Innate Cytokine Responses Induced by Lactobacilli Colonization and Human Rotavirus Infection in Gnotobiotic Pigs.
Wen K., Azevedo M., Gonzalez A., Zhang W., Saif L., Li G., Yousef A., and Yuan L.
Vet Immunol Immunopathol. 2009, 127(3-4):304-315.
Probiotic Lactobacillus Acidophilus Enhances the Immunogenicity of an Oral Rotavirus Vaccine in Gnotobiotic Pigs.
Zhang W., Azevedo M., Wen K., Gonzalez A., Saif L., Yousef A., and Yuan L.
Vaccine. 2008, 26(29-30):3655-3661.
Virus-Specific Intestinal IFNγ Producing T Cell Responses Induced by Human Rotavirus Infection and Vaccines are Correlated with Protection Against Rotavirus Diarrhea in Gnotobiotic Pigs.
Yuan L., Wen K., Azevedo M., Gonzalez A., Zhang W., and Saif L.
Vaccine. 2008, 26(26):3322-3331.
Contact information for all lab members:
Seongwon Nho, Ph.D.
Sharmily Khanam, Ph.D.
- Contact Information
- Marli Azevedo
- (870) 543-7121
ExpertiseApproachDomainTechnology & DisciplineToxicology