# Host Cell Receptor and Herpes Simplex Virus 1 Glycoprotein B Are Determinants of Low Temperature Entry

## TL;DR

This study identifies host cell receptors and viral proteins that determine how herpes simplex virus 1 enters cells at low temperatures.

## Contribution

The study reveals that nectin-2 and glycoprotein B (gB) are key determinants of HSV-1 entry at low temperatures.

## Key findings

- Nectin-2, but not nectin-1, mediates HSV-1 ANG path entry at 4°C in CHO-K1 cells.
- HSV-1 strain KOS and ANG path enter HaCaT cells at 4°C, but a gB-containing chimera does not.
- Low temperature HSV-1 entry depends on cell type and involves multiple determinants.

## Abstract

Herpes simplex virus 1 (HSV-1) entry is a complex interplay of viral and host factors. The mechanisms of its regulation remain undefined. HSV-1 entry occurs via multiple distinct and cell-type dependent pathways, further complicating study of this process. HSV-1 strains with atypical entry properties aid in the elucidation of entry determinants. HSV-1 strain ANG path exhibits entry in Vero cells at 4 °C, whereas wild-type strains do not. We investigated the determinants of low temperature entry by HSV-1 ANG path in several cell types. The receptor nectin-2 mediated 4 °C entry of HSV-1 ANG path into CHO-K1 cells, but the related receptor nectin-1 did not, suggesting that gD-binding receptors are a determinant of HSV-1 entry at low temperatures. In HaCaT cells, both HSV-1 ANG path and wild-type strain KOS entered at 4 °C, while HSV-1 chimera 27/III, which contains KOS strain gB in the ANG path virus background, did not. This suggests that gB functions as a determinant of low temperature entry of HSV-1. Together, the findings suggest that there are multiple determinants and mechanisms of HSV-1 low temperature entry and that the requirements differ by cell type.