Journal article
Cellular and viral requirements for rapid endocytic entry of herpes simplex virus
Journal of virology, Vol.78(14), pp.7508-7517
07/2004
Handle:
https://hdl.handle.net/2376/105868
PMCID: PMC434080
PMID: 15220424
Abstract
It was recently demonstrated that herpes simplex virus (HSV) successfully infects Chinese hamster ovary (CHO) cells expressing glycoprotein D (gD) receptors and HeLa cells by an endocytic mechanism (A. V. Nicola, A. M. McEvoy, and S. E. Straus, J. Virol. 77:5324-5332, 2003). Here we define cellular and viral requirements of this pathway. Uptake of intact, enveloped HSV from the cell surface into endocytic vesicles was rapid (t(1/2) of 8 to 9 min) and independent of the known cell surface gD receptors. Following uptake from the surface, recovery of intracellular, infectious virions increased steadily up to 20 min postinfection (p.i.), which corresponds to accumulation of enveloped virus in intracellular compartments. There was a sharp decline in recovery by 30 min p.i., suggesting loss of the virus envelope as a result of capsid penetration from endocytic organelles into the cytosol. In the absence of gD receptors, endocytosed virions did not successfully penetrate into the cytosol but were instead transported to lysosomes for degradation. Inhibitors of phosphatidylinositol (PI) 3-kinase, such as wortmannin, blocked transport of incoming HSV to the nuclear periphery and virus-induced gene expression but had no effect on virus binding or uptake. This suggests a role for PI 3-kinase activity in trafficking of HSV through the cytosol. Viruses that lack viral glycoproteins gB, gD, or gH-gL were defective in transport to the nucleus and had reduced infectivity. Thus, similar to entry via direct penetration at the cell surface, HSV entry into cells by wortmannin-sensitive endocytosis is efficient, involves rapid cellular uptake of viral particles, and requires gB, gD, and gH-gL.
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Details
- Title
- Cellular and viral requirements for rapid endocytic entry of herpes simplex virus
- Creators
- Anthony V Nicola - Medical Virology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1888, USA. anicola@niaid.nih.govStephen E Straus
- Publication Details
- Journal of virology, Vol.78(14), pp.7508-7517
- Academic Unit
- Veterinary Microbiology and Pathology, Department of
- Publisher
- United States
- Identifiers
- 99900546814501842
- Language
- English
- Resource Type
- Journal article