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Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient Reactivation

English version České info

Although mouse models have been very useful in studies of HSV1 latency, the inability to efficiently reactivate latent HSV1 in vivo has impeded studies of reactivation. Reasoning that reactivation would be much more efficient in the absence of T cells, we exploited IVIG to promote survival of latently infected Rag mice lacking B and T cells. We established a threshold inoculum dose that was higher for B6 -⁠ compared to 129-Rag mice, which determined whether HSV1 could be efficiently reactivated in vivo resulting in encephalitis. We showed directly that memory T cells are required to control spontaneous and induced reactivation in mice inoculated at high dose but are dispensable for maintaining latency in low dose inoculated mice. Incorporating different knockout strains into the Rag latency model by adoptive transfer of cells or crossbreeding will facilitate studying the role of various cellular genes involved in regulating neuronal gene expression and innate and adaptive immunity in the control of HSV1 reactivation. The potential of this powerful latency model to unravel the molecular and immune mechanisms regulating latency will be realized only after it is adopted and refined by researchers in the field.

Vyšlo v časopise: Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient Reactivation. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004730
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004730

Souhrn

Although mouse models have been very useful in studies of HSV1 latency, the inability to efficiently reactivate latent HSV1 in vivo has impeded studies of reactivation. Reasoning that reactivation would be much more efficient in the absence of T cells, we exploited IVIG to promote survival of latently infected Rag mice lacking B and T cells. We established a threshold inoculum dose that was higher for B6 -⁠ compared to 129-Rag mice, which determined whether HSV1 could be efficiently reactivated in vivo resulting in encephalitis. We showed directly that memory T cells are required to control spontaneous and induced reactivation in mice inoculated at high dose but are dispensable for maintaining latency in low dose inoculated mice. Incorporating different knockout strains into the Rag latency model by adoptive transfer of cells or crossbreeding will facilitate studying the role of various cellular genes involved in regulating neuronal gene expression and innate and adaptive immunity in the control of HSV1 reactivation. The potential of this powerful latency model to unravel the molecular and immune mechanisms regulating latency will be realized only after it is adopted and refined by researchers in the field.

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Článek Adhesive Fiber Stratification in Uropathogenic Biofilms Unveils Oxygen-Mediated Control of Type 1 Pili
Článek Vaccinia Virus Protein Complex F12/E2 Interacts with Kinesin Light Chain Isoform 2 to Engage the Kinesin-1 Motor Complex
Článek Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis
Článek Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax Requires CADM1/TSLC1 for Inactivation of the NF-κB Inhibitor A20 and Constitutive NF-κB Signaling
Článek Suppression of RNAi by dsRNA-Degrading RNaseIII Enzymes of Viruses in Animals and Plants
Článek Spatiotemporal Regulation of a T4SS Substrate by the Metaeffector SidJ
Článek Antigenic Properties of the Human Immunodeficiency Virus Envelope Glycoprotein Gp120 on Virions Bound to Target Cells
Článek Dependence of Intracellular and Exosomal microRNAs on Viral Oncogene Expression in HPV-positive Tumor Cells
Článek Identification of a Peptide-Pheromone that Enhances Escape from Host Cell Vacuoles
Článek Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased Endothelial Activation
Článek Transgenic Expression of the Dicotyledonous Pattern Recognition Receptor EFR in Rice Leads to Ligand-Dependent Activation of Defense Responses
Článek Comprehensive Antigenic Map of a Cleaved Soluble HIV-1 Envelope Trimer
Článek Low Doses of Imatinib Induce Myelopoiesis and Enhance Host Anti-microbial Immunity
Článek Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Oxidized Biopterins in Pediatric Falciparum Malaria: Association with Disease Severity
Článok vyšiel v časopise

PLOS Pathogens

2015 Číslo 3
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Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
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