Herpes Simplex Virus Type 1 Glycoprotein E Domains Involved in Virus Spread and Disease

Abstract

Herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) functions as an immunoglobulin G (IgG) Fc binding protein and is involved in virus spread. Previously we studied a gE mutant virus that was impaired for IgG Fc binding but intact for spread and another that was normal for both activities. To further evaluate the role of gE in spread, two additional mutant viruses were constructed by introducing linker insertion mutations either outside the IgG Fc binding domain at gE position 210 or within the IgG Fc binding domain at position 380. Both mutant viruses were impaired for spread in epidermal cells in vitro; however, the 380 mutant virus was significantly more impaired and was as defective as gE null virus. gE mutant viruses were inoculated into the murine flank to measure epidermal disease at the inoculation site, travel of virus to dorsal root ganglia, and spread of virus from ganglia back to skin to produce zosteriform lesions. Disease at the inoculation and zosteriform sites was reduced for both mutant viruses, but more so for the 380 mutant virus. Moreover, the 380 mutant virus was highly impaired in its ability to reach the ganglia, as demonstrated by virus culture and realtime quantitative PCR. The results indicate that the domain surrounding amino acid 380 is important for both spread and IgG Fc binding and suggest that this domain is a potential target for antiviral therapy or vaccines.

Two Modes of Pseudorabies Virus Neuroinvasion and Lethality in Mice

“…During the acclimation period and throughout the course of the experiment, the mice were maintained under constant ambient temperature and photoperiod conditions (12 h of light, 12 h of darkness). The protocol used for the mouse flank inoculation was adapted from the protocol described by Simmons and Nash (25) and Friedman and coworkers (24,29). The mice each weighed ϳ17 g and were anesthetized with an intraperitoneal (i.p.)…”

“…PRV first replicates at the site of inoculation and then spreads into the PNS via the sensory and motor nerve endings innervating the skin. In the HSV mouse flank model, infection then spreads from the ganglia out to secondary skin sites within the dermatome (zosteriform spread) (24,25). To compare the spread of the virulent, mutant, and attenuated PRV strains, various peripheral and CNS tissues were selected at intervals postinoculation for titer assay of infectious virus.…”

“…The U S 9, gE, and gI gene products are not required for spread in the retrograde direction. In addition, in virulent PRV strains, the gE and gI proteins play significant roles in promoting the characteristic symptoms of PRV infection and rapid death (32).We used a flank scarification method of PRV inoculation previously described for other alphaherpesviruses (24,25). The mouse flank infection model emulates a naturally occurring alphaherpesvirus infection in that infection is initiated in epithelial tissue, followed by spread of virus to the PNS, with the potential for further progression into structures of the CNS.…”

“…We used a flank scarification method of PRV inoculation previously described for other alphaherpesviruses (24,25). The mouse flank infection model emulates a naturally occurring alphaherpesvirus infection in that infection is initiated in epithelial tissue, followed by spread of virus to the PNS, with the potential for further progression into structures of the CNS.…”

Function of glycoprotein E of herpes simplex virus requires coordinated assembly of three tegument proteins on its cytoplasmic tail

“…Moreover, it requires glycoproteins E and I (gE and gI, respectively) (1), which are not necessary for "cell-free" transmission (3). Consequently, HSV mutants lacking gE/gI are severely restricted for spread to neuronal cells (3)(4)(5)(6)(7)(8)(9)(10)(11). Remarkably, along with the core entry proteins, the gE/gI heterodimer is also required for HSV-induced cell fusion to produce syncytia (3,12,13).…”