The soluble amino-terminal region of HVEM mediates efficient herpes simplex virus type 1 infection of gD receptor-negative cells.

Abstract

BACKGROUND:

Previous studies from our own and other labs reported the surprising finding that the soluble V domain of the herpes simplex virus type 1 (HSV-1) entry receptor nectin-1 can both block HSV infection of receptor-bearing cells and mediate infection of receptor-deficient cells. Here we show that this property is not unique to nectin-1. We generated a pair of truncated, soluble forms of the other major HSV-1 entry receptor, herpes virus entry mediator (HVEM or HveA), and examined its effects on HSV-1 infection of receptor-deficient cells.

RESULTS:

In cultures of CHO-K1 cells, sHveA102 comprising the two amino-terminal cysteine-rich pseudorepeats (CRPs) of HVEM enabled infection of greater than 80% of the cells at an MOI of 3, while sHveA162 comprising the complete ectodomain failed to mediate infection. Both sHveA102 and sHveA162 blocked infection of CHO-K1 cells stably expressing HVEM in a dose-dependent manner, indicating that both were capable of binding to viral gD. We found that sHveA102-mediated infection involves pH-independent endocytosis whereas HSV infection of HVEM-expressing CHO-K1 cells is known to be pH-dependent.

CONCLUSIONS:

Our results suggest that the C-terminal portion of the soluble HVEM ectodomain inhibits gD activation and that this effect is neutralized in the full-length form of HVEM in normal infection.

• Authors: Hyunjung Baek, Jae Hong Kim, Yoon Tae Noh, Heechung Kwon
• Journal: Virology journal (Virol J) Vol. 9 Pg. 15 (Jan 13 2012) ISSN: 1743-422X [Electronic] England
• PMID: 22239829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Tumor Necrosis Factor, Member 14
• Receptors, Virus
• TNFRSF14 protein, human
• Viral Envelope Proteins
• glycoprotein J, herpesvirus simiae

Topics

• Animals
• CHO Cells
• Chlorocebus aethiops
• Cricetinae
• Cricetulus
• Herpesvirus 1, Human (physiology)
• Humans
• Protein Binding
• Receptors, Tumor Necrosis Factor, Member 14 (metabolism)
• Receptors, Virus (metabolism)
• Vero Cells
• Viral Envelope Proteins (metabolism)
• Virus Internalization