# Measles virus infection of the respiratory tract

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Measles is increasing as a cause of morbidity and mortality worldwide. Measles virus (MeV), the causative
agent of measles, is spread by the respiratory route and is one of the most highly infectious viruses of humans
with an estimated basic reproductive rate (R0) of 12-18 that drives the need for high levels of population
immunity to prevent outbreaks. Measles is a human disease, but macaques can contract measles through
contact with humans, develop disease that mimics human measles and have been effectively used for studies
of measles pathogenesis. Understanding the extremely efficient airborne transmission of MeV requires
knowledge of both the initiation of infection after viral aerosol or droplet contact with the respiratory tract and
mechanisms of virus control and release. Respiratory epithelial cells were long assumed to be the first site of
MeV infection with subsequent spread to lymphoid tissue. However, investigators using enhanced green
fluorescent protein (eGFP)-expressing recombinant reporter MeVs were not able to detect infected respiratory
epithelial cells early after infection of macaques or to demonstrate infection from the apical surface of
differentiated respiratory epithelial cells in culture and deduced that they had not become infected. Because
eGFP-expressing cells were observed after basal infection of cultured epithelial cells, an alternate view
emerged that lung epithelial cell infection is initiated through basolateral exposure to infected lymphocytes and
does not occur until after the viremia is established. These latter studies have concluded that myeloid cells
rather than epithelial cells are the initial sites of MeV infection in the lung. However, our data show that apical
infection of respiratory epithelial cells is actually quite efficient, but exposure to MeV induces shedding of MeV-
producing multinucleated giant cells from the epithelial surface and leaves it without detectable infected cells.
Therefore, epithelial cells may be important for the initiation as well as dissemination of MeV infection.
Identification of the susceptible cells in the respiratory tract that allow for very efficient initiation of infection and
determination of the mechanism of MeV entry into differentiated epithelial cells are key to understanding
efficient MeV transmission and use aerosolized vaccine for measles immunization. To address this critical area
we will use in vitro and in vivo studies of rhesus macaques to identify the mechanisms by which both wild type
and vaccine strains of MeV infect primary differentiated respiratory tract epithelial cells through the following
specific aims: (1) Determine the relative susceptibility to infection with MeV of primary alveolar macrophages
and cultures of differentiated cells from the upper and lower respiratory tract that include lung fibroblasts,
dendritic cells and basal, ciliated and mucous-producing epithelial cells. (2) Determine the host receptors used
and mechanisms by which MeV in...

## Key facts

- **NIH application ID:** 10030808
- **Project number:** 1R01AI153140-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Diane E Griffin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 1
- **Project period:** 2020-05-04 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10030808

## Citation

> US National Institutes of Health, RePORTER application 10030808, Measles virus infection of the respiratory tract (1R01AI153140-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10030808. Licensed CC0.

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