Research

We are currently focused on three aspects of viruses and how they interact with the host

  1. How do viruses enter cells? How do they maintain responsiveness to host factors and receptors, while protecting functional centers from attack by antibodies?
  2. How does the host adaptive immune response overcome virus’s evolved mechanisms of immune evasion?
  3. How do small pieces of the viral RNA serve multiple functions? How do viral RNA genomes regulate many aspects of the viral replication cycle?

We aim to answer these questions through the biophysical interrogation of the conformational and compositional dynamics of viral macromolecules.

Toward a dynamics-based description of viral envelope glycoprotein function

Enveloped viruses enter cells by fusing the viral membrane with a cellular membrane. The energy needed to fuse membranes is contained entirely within the metastable conformation of viral envelope glycoproteins, which reside on the surface of the virion. This energy is liberated through a cascade of conformational changes that ultimately bring the viral and cellular membranes together.

Representative publications:

Direct visualization of the conformational dynamics of single hemagglutinin trimers

Das DK, Govindan R, Nikic-Spiegel I, Krammer F, Lemke EA, & Munro JB

Cell 174: 926-937

2018

Pubmed Link

Viral immune evasion by conformational masking

Viral envelope glycoproteins are the primary targets of the host antibody response. We develop biophysical methodologies to understand how envelope glycoproteins conceal functional centers from attack by antibodies while maintaining responsiveness to cellular cues that trigger membrane fusion.

Representative publications:

Real-Time Analysis of Individual Ebola Virus Glycoproteins Reveals Pre-Fusion, Entry-Relevant Conformational Dynamics

Durham ND, Howard AR, Govindan R, Senjobe F, Fels JM, Diehl WE, Luban J, Chandran K, & Munro JB

Viruses 12: 1

2020

Pubmed Link

RNA dynamics during regulation of virus replication

RNA structure is intimately involved in the regulation of virus replication. RNAs of modest size can have multiple functional roles by adopting distinct conformations at different steps of the replication cycle. We develop biophysical tools to probe these dynamics and understand the viral and cellular factors that shape RNA structure and conformation.

Representative publications:

Stability and conformation of the dimeric HIV-1 genomic RNA 5’UTR

Blakemore RJ, Burnett C, Swanson C, Kharytonchyk S, Telesnitsky A, and Munro JB

Biophysical Journal 120: 4874

2021

Pubmed Link