The Requirement of Glycoprotein C for Interindividual Spread Is Functionally Conserved within the Alphaherpesvirus Genus (Mardivirus), but Not the Host (Gallid)

Abstract

Marek’s disease (MD) in chickens is caused by Gallid alphaherpesvirus 2, better known as MD herpesvirus (MDV). Current vaccines do not block interindividual spread from chicken-to-chicken, therefore, understanding MDV interindividual spread provides important information for the development of potential therapies to protect against MD, while also providing a natural host to study herpesvirus dissemination. It has long been thought that glycoprotein C (gC) of alphaherpesviruses evolved with their host based on their ability to bind and inhibit complement in a species-selective manner. Here, we tested the functional importance of gC during interindividual spread and host specificity using the natural model system of MDV in chickens through classical compensation experiments. By exchanging MDV gC with another chicken alphaherpesvirus (Gallid alphaherpesvirus 1 or infectious laryngotracheitis virus; ILTV) gC, we determined that ILTV gC could not compensate for MDV gC during interindividual spread. In contrast, exchanging turkey herpesvirus (Meleagrid alphaherpesvirus 1 or HVT) gC could compensate for chicken MDV gC. Both ILTV and MDV are Gallid alphaherpesviruses; however, ILTV is a member of the Iltovirus genus, while MDV is classified as a Mardivirus along with HVT. These results suggest that gC is functionally conserved based on the virus genera (Mardivirus vs. Iltovirus) and not the host (Gallid vs. Meleagrid).

The Conserved Herpesviridae Protein Kinase (CHPK) of Gallid alphaherpesvirus 3 (GaHV3) Is Required for Horizontal Spread and Natural Infection in Chickens

“…We previously developed a tool to track 301B/1 in cell culture and chickens [ 54 ]. We hypothesized that 301B/1 CHPK activity, like MDV CHPK activity, would be essential for horizontal transmission in chickens.…”

“…The parental virus in which 301B/1 expressing monomeric red fluorescent protein (mRFP) fused to pUL47 (pUL47mRFP) has been previously described [ 54 ]. The invariant lysine (K157) of 301B/1 was mutated to an alanine (A) to generate a CHPK mutant clone (rCHPKmut) using two-step Red-mediated mutagenesis in GS1783 Escherichia coli cells.…”

“…Statistical significance was declared at p < 0.05 and the mean tests associated with significant interactions (p < 0.05) were separated with Tukey's tests. We previously developed a tool to track 301B/1 in cell culture and chickens [54]. We hypothesized that 301B/1 CHPK activity, like MDV CHPK activity, would be essential for horizontal transmission in chickens.…”

Coinfection in the host can result in functional complementation between live vaccines and virulent virus

“…Following inoculation, viruses were back tittered and were as follows: For Experiment 1, 2,000 and 7,000 plaque forming units (PFU) of non-transmissible MDV (MDV-NT) and transmissible MD vaccine (vacMD-T), respectively, were inoculated into chicks, while in Experiment 2, 3,000 and 6,000 PFU of MDV-NT and non-transmissible MD vaccine (vacMD-NT), respectively, were used. The higher dose of vacMD used was based on previous studies in which this vaccine requires higher doses that MDV for establishing infection [ 18 , 21 ].…”

Special Issue “Replication and Spread of Alphaherpesviruses”

“…Two primary research articles also deal with host-host spread, in this case of avian alphaherpesviruses. The article by Vega-Rodriguez et al [5] focuses on Marek's disease virus (MDV) and an MDV glycoprotein, gC, that is required for transmission between chicken hosts. The authors investigate whether gC homologs from related alphaherpesviruses can substitute for MDV gC in mediating spread.…”