Anna Kloc, Ph.D.
Post-doctoral training, United States Department of Agriculture – Plum Island Animal Disease Center and Yale University School of Medicine
Ph.D., Genetics, Stony Brook University
B.A., Biology, Hunter College
Heart disease, myocarditis, viral replication and immune system response to viral infection
Heart disease is the leading cause of death in the USA. The Center for Disease Control and Prevention estimates that half of adults in the USA will experience cardiac disease in their lives, and 1 in 4 people will die of heart-related issues. One of the reasons behind human heart malfunction is infection with viruses, which manifests itself as inflammation, known as myocarditis. People who suffer from this disease experience shortness of breath or arrhythmias, and severe cases of myocarditis may lead to heart failure. To date, many human viruses, such as Parvovirus B19, Coxsackievirus B3, or Epstein-Barr virus, have been associated with myocarditis. Yet, the processes of viral infection, the subsequent activation of the immune system, and the ability of the host to clear the infection, are not fully understood.
In order to infect human heart, a viral particle must enter a cardiac cell, rapidly amplify its genome and produce infectious progeny, all while avoiding the host defense mechanisms. Viral replication is a highly regulated process that involves the interaction between viral proteins and host proteins to manipulate different cellular pathways in favor of virus survival. At the same time, the infected organism activates the immune system response to the virus to counteract the infection. The competition between the virus and the host immune response ultimately determines the outcomes of viral disease. Therefore, understanding how the virus replicates in the host is critical for the design of both antiviral drug strategies, and for vaccine development.
Our laboratory combines molecular biology and virology approaches to investigate the immune system response in human heart tissue samples infected with viruses. We are interested in an in-depth characterization of gene expression patterns that underlie virus-induced heart inflammation. Furthermore, we utilize sequencing methods to uncover any mutation(s) in the viral genomes that may make it more likely for a virus to infect the human heart, or escape the immune system response. These analyses could help us better understand the role of viral infections in heart pathology.
Diaz-San Segundo F, Medina GN, Spinard E, Kloc A, Ramirez-Medina E, Azzinaro P, Mueller S, Rieder E, de los Santos T Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus. Frontiers in Microbiology, 21 January 2021, 11: 610286
Kloc A, Rai DK, Gladue DP, Schafer E, Kenney M, Rieder E Residues within the Foot-and-Mouth Disease Virus 3Dpol Nuclear Localization Signal Affect Polymerase Fidelity. Journal of Virology, 2020 Aug 17;94(17)
Kloc A, Rai DK, Rieder E The Roles of Picornavirus Untranslated Regions in Infection and Innate Immunity. Frontiers in Microbiology, 2018 March 20;9:485
Kloc A, Diaz-San Segundo F, Schafer E, Rai DK, Keeney M, de los Santos T, Rieder E Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells. Virology, 2017 Sep 26;512:132-143
Rai DK, Diaz-San Segundo F, Campagnola G, Keith A, Schafer EA, Kloc A, de Los Santos T, Peersen O, Rieder E Attenuation of Foot-and-Mouth Disease Virus by Engineering Viral Polymerase Fidelity. Journal of Virology, 2017 Jun12;91(15)
Medina GN, Knudsen GM, Greninger AL, Kloc A, Diaz-San Segundo F, Rieder E, Grubman MJ, DeRisi JL, de Los Santos T Interaction between FMDV Lpro and transcription factor ADNP is required for optimal viral replication. Virology, 2017 May;505:12-22
Rai DK, Lawrence P, Kloc A, Schafer E, Rieder E Analysis of the interaction between host factor Sam68 and viral elements during foot-and-mouth disease virus infection. Virology Journal, 2015 Dec 23;12(1):224
Kloc A, Ivanova N Chromatin and Pluripotency: the MYSTerious connection. Cell Stem Cell, 2012 Aug 3; 11(2):139-40
Zaratiegui M, Castel S, Irvine D, Kloc A, Ren J, Li F, de Castro E, Martin L, Chang AY, Goto D, Cande WZ, Antequera F, Acrangioli B, Martienssen RA RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II. Nature, 2011 Oct 16; 476(7371):135-8
Martienssen RA, Kloc A, Slotkin RK, Tanurdzić M Epigenetic inheritance and reprogramming in plants and fission yeast. Cold Spring Harbor Symposium Quantitative Biology, 2008;73:265-71
Kloc A and Martienssen R RNAi, heterochromatin and the cell cycle. Trends in Genetics, 2008 Oct; 24(10):511-7
Kloc A, Zaratiegui M, Nora E, Martienssen R RNA interference guides histone modification during the S phase of chromosomal replication. Current Biology, 2008 Apr 8;18(7) 490-5