Developing New Tissue-Based Models for the Study of Mumps Virus Infection in Humans

  • Lim, Jean (PI)

Project Details

Description

Mumps virus (MuV) is a highly contagious virus that is characterized by the painful enlargement of the salivary glands. Prior to vaccination, mumps was a disease primarily in children, but in the post-vaccination era, the majority of cases have occurred in young adults between the ages of 15-24, primarily due to the waning of vaccine-induced immunity. Interestingly, because MuV is spread by respiratory droplets, direct contact with infected individuals, or contaminated objects, modern mumps outbreaks typically occur in living situations where an infected individuals is in close contact with numerous other individuals, including the military. In fact, every infected individual is estimated to cause 10-12 secondary cases. Outbreaks are also exacerbated by the fact that individuals are highly contagious before the appearance of clinical symptoms. In the US, a country with high MuV vaccination rates, there are still hundreds to thousands of mumps cases annually. Worldwide cases of mumps occur that can number in the tens of thousands (World Health Organization), depending on the year, including many countries where military personnel are stationed, placing those individuals and their families at risk.

Particularly in the post-vaccine era, very little attention has been given to the study of MuV. This is because there are no small animal models to study pathogenesis, and information obtained from in vitro studies is limited. In this application, we seek to learn more about how MuV causes disease in humans and understand more about the antibody response generated against the mumps portion of the MMR (measles, mumps, rubella) vaccine. We will take advantage of recent advances in reverse genetics systems to generate MuV expressing reporter genes to establish new models of infection using human whole tissues to mimic viral replication of MuV in salivary glands and human lymph nodes (Aim 1). Using these models, we will identify the infected cells in these whole organ systems using a relatively new RNA sequencing technique (Aim 2). Finally, we will characterize the antibody response generated against the MuV in the general US population by screening a large cohort of US blood donors collected through the American Red Cross (nearly all vaccinated with MMR) with the ultimate goal of identifying those individuals at risk of infection with MuV (Aim 3).

This research will be important in identifying virus:host interactions that could be used to study how the virus interacts with the host in key organs involved in its pathogenesis, which will provide novel intervention strategies that could be exploited for antivirals and therapeutics. We will also screen the general US population for antibodies generated against MuV. This will provide a large-scale understanding of the distribution of antibody responses in the US according to age, sex, and geographic area. Eventually, these samples can be compared to a population of individuals who contracted mumps during an outbreak, as well as after receiving a mumps vaccine boost to determine how the antibody response has changed. All of these data will be of great value in understanding how MuV causes disease and who may be at risk for infection, despite prior vaccination.

StatusActive
Effective start/end date1/01/19 → …

Funding

  • Congressionally Directed Medical Research Programs: $339,000.00

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