Host Enzymes Heparanase and Cathepsin L Promote Herpes Simplex Virus 2 Release from Cells

Journal of Virology
James HopkinsDeepak Shukla

Abstract

Herpes simplex virus 2 (HSV-2) can productively infect many different cell types of human and nonhuman origin. Here we demonstrate interconnected roles for two host enzymes, heparanase (HPSE) and cathepsin L, in HSV-2 release from cells. In vaginal epithelial cells, HSV-2 causes heparan sulfate shedding and upregulation in HPSE levels during the productive phase of infection. We also noted increased levels of cathepsin L and show that regulation of HPSE by cathepsin L via cleavage of HPSE proenzyme is important for infection. Furthermore, inhibition of HPSE by a specific inhibitor, OGT 2115, dramatically reduces HSV-2 release from vaginal epithelial cells. Likewise, we show evidence that the inhibition of cathepsin L is detrimental to the infection. The HPSE increase after infection is mediated by an increased NF-κB nuclear localization and a resultant activation of HPSE transcription. Together these mechanisms contribute to the removal of heparan sulfate from the cell surface and thus facilitate virus release from cells.IMPORTANCE Genital infections by HSV-2 represent one of the most common sexually transmitted viral infections. The virus causes painful lesions and sores around the genitals or rectum. Intermittent release of t...Continue Reading

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Citations

Dec 13, 2019·Journal of Virology·Satvik HadigalDeepak Shukla
Jul 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Olga TarasovaVladimir Poroikov
Aug 28, 2020·Eye·Daniel Sibley, Daniel F P Larkin
May 29, 2020·Cellular and Molecular Life Sciences : CMLS·Raghuram KogantiDeepak Shukla
Oct 30, 2019·Microorganisms·Raghuram KogantiDeepak Shukla
Feb 10, 2021·Antibiotics·Floriana D'AngeliRosaria Acquaviva
Dec 29, 2020·Frontiers in Cellular and Infection Microbiology·Caio P GomesJoão Bosco Pesquero
Apr 15, 2021·Seminars in Thrombosis and Hemostasis·Raghuram KogantiDeepak Shukla
Jun 17, 2021·Bioscience Reports·Safa KinanehShadi Hamoud

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