Maria Kalamvoki, Ph.D.
Microbiology, Molecular Genetics & Immunology
Ph.D., Kapodistrian University of Athens, Greece & Hellenic Pasteur Institute
Postdoctoral Scholar, University of Chicago, Department of Microbiology
Following the primary infection with herpes simplex viruses (HSV-1 or HSV-2), latent infections are established in sensory ganglia. Periodically the virus reactivates from the sensory ganglia and is then excreted at a site of or near the portal of entry into the body. The consequences of reactivation range from annoying labialis, genital sores or blisters, to blindness caused by herpes keratitis, increased susceptibility to HIV-1 infection and increased likelihood of HSV transmission to contacts, and the risk of developing encephalitis especially in immunocompromised individuals. Transmission to newborns may cause death or severe neurological damage. There is no cure for herpes. The current antiviral drugs, acyclovir, valaciclovir and famciclovir, can prevent or shorten outbreaks during the period of time the patient is under medication. Drug resistance is evident in immunocompromised patients such as in patients with AIDS and recipients of bone marrow transplants.
My research interest centers on mechanisms by which the Herpes Simplex Viruses (HSV) combat host defenses and utilize host cellular machineries to efficiently replicate and spread.
The projects on which my lab focuses emanated from studies exploring the interactions of HSV-1 with the innate immune component STING (STimulator of Interferon Genes). STING is widely known as a cytoplasmic DNA sensor, which is activated by a broad spectrum of pathogens and subsequently activates type-I Interferon and proinflammatory responses. STING restricts HSV replication. While STING is generally considered hostile to the virus, we found that HSV actively stabilizes STING. Moreover, we found that during infection STING, along with viral and host macromolecules, are released from the infected cells in exosomes and delivered to target cells. This intercellular transfer largely relies on exosomes. A reasonable hypothesis is that the virus modifies the exosomal cargo to include components, such as STING, whose function controls the virus dissemination. The nature and functions of exosomes produced during herpes simplex virus infection are currently under investigation in my lab. Positions for students and other researchers are available.
Kalamvoki M, Deschamps T., Extracellular vesicles during Herpes Simplex Virus type 1 infection: an inquire.Virol J. 2016 Apr 5;13(1):63. doi: 10.1186/s12985-016-0518-2. Review. PMID: 27048572
Kalamvoki M, Du T and Roizman B., Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING and viral mRNAs and miRNAs. PNAS 2014 Nov 18; 111(46): E4991-6. PMCID: PMC4246290.
Kalamvoki M and Roizman B., HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the Us3 protein kinase and cell type. PNAS 2014 Feb 4; 111(5): E611-7.PMCID: PMC3918790.
Kalamvoki M and Roizman B., The histone acetyl transferase CLOCK is an essential component of the herpes simplex virus 1 transcriptome that includes TFIID, ICP4, ICP27, and ICP22, J. Virol. Sep 85(18):9472-9477, 2011. PMCID: PMC3165755.
Kalamvoki M and Roizman B., Circadian CLOCK histone acetyl transferase localizes at ND10 nuclear bodies and enables herpes simplex virus gene expression, PNAS, 107(41): 17721-26, 2010. PMCID: PMC2955081.
Kalamvoki M and Roizman B., ICP0 enables and monitors the function of D cyclins in herpes simplex virus 1 infected cells. PNAS. 106(34):14576-80, 2009, PMCID: PMC2732861.
Kalamvoki M and Roizman B., Nuclear retention of ICP0 in cells treated with HDAC inhibitor or transfected with DNA before infection with herpes simplex virus 1. PNAS, 105(51), 20488-20493, 2008, PMCID: PMC2629265.