Research

Papersmiriam_papers.html
Teachingmiriam_courses.html

Miriam Cohen

micohen@ucsd.edu

Gagneux Lab
Cellular and Molecular Medicine, UCSDGagneux_Lab_UCSD.html
 

I am interested in molecular recognition

and initial interactions of pathogens,

hosts and extracellular matrix

I study the interactions between Influenza A virus and the mucus layer covering the host target tissues. In order to infect, Influenza A virus needs to penetrate a thick layer of mucus, which contains sialylated mucins polymers. These mucins present “decoy” sialic acid ligands for the virus, when the virus binds to these decoys it gets stuck in the mucus. However, influenza virus can cleave sialic acids and free itself from the mucus. Inhibiting neuraminidase activity increases the ability of mucus to trap influenza virus and prevent infection.


The virus envelope is covered with hemagglutinin trimmers with large patches of neuraminidase tetramers. This suggests that the binding and cleaving of sialylated mucins may result directional movement of the virus through the mucus. In addition, influenza infection may dramatically change mucus properties by decreasing sialylation, and thus can promote co-infection with another pathogen. Simultaneous infection with multiple influenza subtypes and in particular co-infection with a drug resistant strains, is a concern, because it can lead to viral re-assortment.


My current project focuses on co-infection of mucus-covered cells by various respiratory pathogens. Co-infection with pandemic and seasonal influenza subtypes may lead to viral reassortment which is a concern. Specifically, the pandemic subtype is sensitive to neuraminidase inhibition, but in contrast the seasonal subtype that is only partially inhibited. I developed fluorescently labeled virus to study the virus transition through the mucus at a single virus resolution, and a novel drug-screening platform using mucus-coated cells. In addition, I investigate the synergism between influenza virus and bacteria such as Streptococcus pneumoniae and Haemophilus influenzae during co-infection of mucus-covered cells.

Miriam Cohen’s Web page: MiriamCohenPhD.com