Host-Pathogen Dynamics

Using cutting edge imaging and spectroscopic technologies combined with novel lipidomic and proteomic approaches, investigations in the Laboratory of Host-Pathogen Dynamics, led by Dr. Nihal Altan-Bonnet, have been at the forefront of understanding the virus-host interface, revealing novel replication and transmission mechanisms shared by many different human viruses.

Nihal Altan-Bonnet

Research Interests

Research Interests

The Laboratory of Host-Pathogen Dynamics is comprised of a multidisciplinary team of investigators combining tools of cell and molecular biology, virology and immunology along with high-resolution imaging to understand how viruses transmit themselves effectively among hosts and establish successful infections.

In particular, my lab has revealed novel roles for host membranes in mediating successful viral replication and transmission.

These include:

  • Elucidating the panviral role host PI4P lipids and cholesterol play in viral RNA replication (Hsu et al., Cell 2010; Ilnystka et al., Cell Host and Microbe 2013)
  • Discovering a novel form of viral transmission between hosts whereby viruses transport themselves in clusters packaged inside extracellular vesicles. We have shown that this, in contrast to moving around as single free viral particles,  enhances viral infectivity and protects viruses from host immune responses (Chen et al., Cell 2015; Santiana et al., Cell Host and Microbe 2018). Our ongoing studies indicate that vesicle-cloaked viral clusters are a unique viral form showing behavior that is apart from typical non-enveloped or enveloped viral particles.
  • Discovering the cellular exit pathway used by Coronaviruses including SARS-CoV2. How coronaviruses got out of cells was a mystery. We have found that these viruses harness lysosomes and use the lysosomal exocytotic pathway to egress from cells and spread to others. Use of this pathway by Coronaviruses ends up disrupting the acidification of lysosomes and leads to perturbation of important lysosomal functions including antigen presentation (Ghosh et al., Cell 2020). Now knowing the pathway by which these viruses get out is leading us to develop targeted antivirals.
  • investigations into post-partum mother-child viral transmission through suckling, and the role of vesicle-cloaked viral clusters in this process.

Images

coronaviruses get out of cells using lysosomes
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Host-Pathogen Dynamics Images

How coronaviruses get out of cells using lysosomes (Ghosh et al., Cell 2020)

Electron micrograph of SARS-COV2 particles inside lysosomes
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Host-Pathogen Dynamics Images

Electron micrograph of SARS-COV2 particles inside lysosomes

viruses travel in clusters inside extracellular vesicles
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Host-Pathogen Dynamics Images

A new form of viral transmission: viruses travel in clusters inside extracellular vesicles ( Santiana et al., Cell Host and Microbe 2018)

Host lipids PI4P, cholesterol are hijacked by RNA viruses to facilitate their replication
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Host-Pathogen Dynamics Images

Host lipids PI4P, cholesterol are hijacked by RNA viruses to facilitate their replication ( Altan-Bonnet., Trends in Cell Biology 2016)

Meet the Team

Nihal Altan-Bonnet

Nihal Altan-Bonnet, Ph.D.

Senior Investigator

Dr. Nihal Altan-Bonnet received her B.A. in biology and chemistry from Hunter College, New York in 1992 and her Ph.D. in cell biology from The Rockefeller University in 1998. She then conducted postdoctoral research with Dr. Jennifer Lippincott-Schwartz at the National Institute of Child Health and Development at the NIH from 1999 to 2005 before receiving a faculty position in the department of biological sciences at Rutgers University. In 2013, Dr. Altan-Bonnet returned to the NIH as an Earl Stadtman Investigator, becoming head of the Laboratory of Host-Pathogen Dynamics at the NHLBI and was promoted to tenured Senior investigator in 2017.  Dr. Altan-Bonnet has been recognized several times for her outstanding research, receiving the  Presidential Early Career Award in Science and Engineering (PECASE) in 2012, being named the John J. Holland lecturer at the American Society of Virology in 2017,  and receiving the Norman Salzman Mentor Award in Virology in 2018. Dr. Altan-Bonnet was also named a Kavli Fellow and Scialog Fellow from 2013-2016. She is an Associate editor at the Molecular Biology of the Cell and is a member of the American Societies for Virology, Microbiology, and Cell Biology.

Manish Kumar

Manish Kumar, Ph.D.

Postdoctoral Fellow
Ashish Mishra

Ashish Mishra, Ph.D.

Postdoctoral Fellow
Adeline

Adeline Kerviel, Ph.D.

Postdoctoral Fellow
Hannah Karen

Hannah Karen Labayo, AMT, ASCPi, Ph.D.

Postdoctoral Fellow
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