Combating Past, Present and Emerging Viruses

Sept. 7, 2021

The COVID-19 pandemic underscored the importance of microorganisms to our lives and health. Inspired by the pandemic, Dr. Arturo Casadevall, Chair of the Academy Governors of the American Academy of Microbiology, invited 3 virologists to present their research at the inaugural Academy Chair of Governors Invited Session at World Microbe Forum. They highlighted scientific advancements that have contributed to a better global understanding of past viral outbreaks, present pandemics and emerging pathogens. As the scientific community at large works to mitigate the current pandemic, the presenters looked to the future of microbiology to focus on the question of 'what's next?' for the field for combating emerging microbial threats.

These speakers spanned the career stages from an inspiring early career researcher to a well-respected Nobel laureate, each bringing a unique and diverse perspective for an array of aspects of virology. The virologists shared the impact of the COVID-19 pandemic on their research discipline and highlighted key takeaways for the future of virology and microbiology.

  • mRNA vaccines are a promising platform for combating current and emerging diseases.

  • New technologies are vital for basic and translational research.

  • New model systems are an exciting frontier to study host-virus interactions.

Translating Basic Science into a Hepatitis C Treatment

In 2020, Academy Fellow Dr. Charles M. Rice was awarded the Nobel Prize in Physiology or Medicine for research on the hepatitis C virus. In 2021, Rice received the ASM Elizabeth O. King Lecture Award for his contributions to public health. For his award lecture, Rice recounted his research career and highlighted the importance of basic research and creation of research tools as the foundation for the eventual development of effective hepatitis C treatments.

In the 1980s, researchers first identified the hepatitis C virus as a RNA virus belonging to the family Flaviviridae. The newly identified virus was a major source of post-transfusion hepatitis, which can lead to chronic liver disease and cirrhosis. Rice, who had previously studied another Flaviviridae virus, yellow fever virus, switched directions to work on the related hepatitis C virus and develop a vaccine for it.

First, Rice’s research group needed to develop a method to replicate the virus in cell culture. After multiple failed attempts, Rice’s group constructed a consensus virus sequence where each nucleotide was determined based on the sequence that was most frequently found in natural hepatitis C viral strains. This consensus strain could infect chimpanzees and allowed for viral replication and study of viral evolution. Building on this work, researchers developed a cell culture system for drug discovery. Rice paralleled his work on hepatitis C with the work on the current COVID-19 pandemic. Just as his and other teams’ research led to hepatitis C treatments, sequencing data, molecular biology and global cooperation allowed for the development of effective COVID-19 diagnostics and therapeutics. Rice noted that continual advances in technology, model systems and research tools will be necessary for connecting foundational knowledge from basic science with widespread applications in public health.

Hepatitis C treatments eliminate the virus and lower the risk of liver disease. Rice stated that in 2015, the cure rate for hepatitis C was 95%. But there is still no vaccine. With the success of messenger RNA (mRNA) vaccines against SARS-CoV-2, Rice was hopeful about the possibility of using this technology in developing future vaccines, both for hepatitis C as well as for yet-to-be-discovered viral pathogens. Rice emphasized that continual investment and research in new vaccine platforms will be vital to tackle current pathogens as well as emerging viral threats of the future.

Informing Influenza and SARS-CoV-2 Vaccine Design

Academy Fellow Dr. Stacey Schultz-Cherry shared her research on 2 other RNA viruses: influenza and SARS-CoV-2. The Schultz-Cherry lab explores the epithelial response to infection, especially in high-risk groups with metabolic conditions such as obesity. The WHO defines obesity as "abnormal or excessive fat accumulation that presents a risk to health," and over 650 million people worldwide are currently considered obese. Schultz-Cherry group’s work to understand how the immune system responds to viruses in obese individuals enables current and future researchers to design effective vaccines against influenza and other viruses for this large population.

Before the COVID-19 pandemic, the world was already dealing with an obesity epidemic. "The most insidious pandemic of the 20th and 21st century has been obesity," said Schultz-Cherry. Excessive fat tissue can release a persistent inflammatory response that taxes the overall immune system. Obese individuals have increased influenza susceptibility, disease severity and death because their immune systems cannot effectively respond to and clear the influenza virus. The Schultz-Cherry research group found body mass index (BMI) positively correlated with viral load and cells from obese individuals have lower immune responses. Building on their previous research, Schultz-Cherry’s group observed a comparable response with SARS-CoV-2 infection where obese animals and humans have more severe COVID-19, and higher BMIs correlate with reduced immune response to infection. Similar to Rice, Schultz-Cherry remarked on the importance of basic research and model systems to examine immune responses and disease severity in diverse populations so as to inform design of treatments, vaccines and public health measures.

However, Schultz-Cherry noticed some significant differences between immunization against SARS-CoV-2 and influenza in this group. While obese individuals show reduced protection from influenza vaccines, current COVID-19 vaccines appear to overcome this challenge. Regardless of BMI, current COVID-19 vaccines induce a "very broad, very strong antibody response." Though both viruses are single-stranded RNA viruses, one major difference is the type of vaccine for each virus. Most COVID-19 vaccines administered in the U.S. are mRNA vaccines, but no mRNA flu vaccine exists. Schultz-Cherry was excited "to see how mRNA technology will translate for flu and if it will get us closer to improved seasonal vaccines" or increase immune responses in individuals with metabolic conditions. She stressed the importance of learning from the science successes of the current COVID-19 pandemic going forward to inform future vaccine design for current viral threats such as influenza.

Modeling Immune Responses to Emerging Viruses

The emergence of SARS-CoV-2 in late 2019 reminded the world of the threat emerging viruses pose. With the possibility of more pathogenic viruses emerging in the future, Dr. Kellie Ann Jurado’s research group examines the regulation of antiviral immune responses to these types of viruses, especially against Zika virus. Jurado shared her research findings to showcase the value of model systems for understanding immune responses to current and possible future viruses. These models will also aid in designing therapeutics to combat these diseases.

Zika, which is transmitted by mosquitos, caused a large outbreak in the Americas in 2015 and previously unknown characteristics of the resultant disease were recognized, including nervous system complications and congenital infection. To understand how Zika virus caused these new symptoms, Jurado used a mouse model deficient for certain immune responses. She showed that the mouse immune response to Zika, and not the Zika infection itself, lead to central nervous system damage and fetal demise. Her work highlighted how adverse host antiviral immune responses can lead to host cell damage.

To balance viral clearance versus immunopathology ("collateral damage"), humans evolved antiviral immune response regulation. This regulation is especially important for nervous and fetal tissue, which are most sensitive to damage. During pregnancy, mothers induce an immunosuppressive environment to tolerate the genetically different fetal and placental tissue. However, studying the immune response in the placenta is very difficult. Jurado explained that rapid technological advancements have paved the way for better and more accurate model systems for difficult-to-study research questions. She noted that the recent developments for models to study the placenta have enhanced the "ability to ask important scientific questions with better, more physiologically relevant models." Using model systems, Jurado’s research team found pregnant mice had high viral loads and no cellular antiviral activity in the placenta, while other infected cells mounted an immune response. They also discovered that specialized placental cell types induce a variety of genes that encode proteins that suppress the antiviral immune response. Jurado hopes researching the immune response to emerging pathogens will allow for a better understanding of human immunology that in turn will allow scientists to develop effective treatments and vaccines.

Fighting Future Pathogens

The COVID-19 pandemic underscored the importance of appreciating knowledge of past pathogens as researchers look forward to discovering and understanding emerging viruses. For SARS-CoV-2, knowledge about SARS-CoV and MERS helped to inform current COVID-19 vaccines. Expanding on past knowledge by using new vaccine platforms, technologies and models will advance the future of science. Looking ahead, the panelists were excited to build on the lessons from COVID-19 and inspire the next generation of microbiologists.

For over half a century, the American Academy of Microbiology and its fellows have been on the forefront of microbiology research. As microbiology has expanded to include new microbes and technologies, so too have Fellows' expertise, sector and background expanded. The Academy and ASM are committed to increasing diversity, equity and inclusion (DEI) in the field of microbiology. This Academy Chair of Governors Invited Session showcased work from both Fellows and outstanding newcomers to the field, helping the Academy shape and propel the future of the microbial sciences.

Author: Rachel Burckhardt, Ph.D.

Rachel Burckhardt, Ph.D.
Dr. Rachel Burckhardt is a scientific literature reviewer for ASM, where she connects scientists to the latest COVID-19 research. Follow her on Twitter @RMBurckhardt.