Measles virus (MeV) is the most contagious human respiratory virus, but within natural hosts MeV infections are largely cell-associated. We recently documented how virus-elicited intercellular pores facilitate rapid MeV spread in well-differentiated primary airway epithelia from human donors. Here we seek to characterize the mechanisms that promote airway epithelium entry and rapid cell-to-cell spread. Our central hypothesis is that MeV developed cell-based strategies for both processes.
In aim 1 we will characterize which myeloid cells transfer infectivity to airway epithelia, and how.
In aim 2 we will identify the cytoskeletal structures and processes co-opted by MeV to promote its rapid epithelial spread. Our studies will reveal how MeV spreads more rapidly than other viruses in human airway epithelia, which accounts for its exceptional contagion efficiency.

Public Health Relevance

Here we seek to better characterize the mechanisms that promote efficient MeV entry in the airway epithelium, and its rapid cell-to-cell spread. Knowledge of these mechanisms is important because they underpin the spread of the most transmissible human respiratory disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI125747-02
Application #
9288122
Study Section
Virology - A Study Section (VIRA)
Program Officer
Park, Eun-Chung
Project Start
2016-06-07
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$194,688
Indirect Cost
$36,875
Name
Mayo Clinic, Rochester
Department
Type
Other Domestic Non-Profits
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Cifuentes-Muñoz, Nicolás; Dutch, Rebecca Ellis; Cattaneo, Roberto (2018) Direct cell-to-cell transmission of respiratory viruses: The fast lanes. PLoS Pathog 14:e1007015
Singh, Brajesh K; Li, Ni; Mark, Anna C et al. (2016) Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells. J Virol 90:6808-6817