Chickens can durably clear herpesvirus vaccine infection in feathers while still carrying vaccine-induced antibodies

Abstract

Marek's disease (MD) is a major disease of chickens induced by Marek's disease virus (MDV) associated to lethal lymphomas. Current MD vaccines protect against lymphomas, but fail to prevent infection and shedding. The control of MDV shedding is crucial in order to eradicate this highly contagious virus. Like pathogenic MDV, MD vaccines infect the feather follicles of the skin before being shed into the environment. MD vaccines constitute excellent models to study virus interaction with feathers, the unique excretion source of these viruses. Herein we studied the viral persistence in feathers of a MD vaccine, the recombinant turkey herpesvirus (rHVT-ND). We report that most of the birds showed a persistent HVT infection of feathers over 41 weeks with moderate viral loads. Interestingly, 20% of the birds were identified as low HVT producers, among which six birds cleared the infection. Indeed, after week 14-26, these birds named controllers had undetectable HVT DNA in their feathers through week 41. All vaccinated birds developed antibodies to NDV, which lasted until week 41 in 95% of the birds, including the controllers. No correlation was found between HVT loads in feathers and NDV antibody titers over time. Interestingly, no HVT DNA was detected in the spleens of four controllers. This is the first description of chickens that durably cleared MD vaccine infection of feathers suggesting that control of Mardivirus shedding is achievable by the host.

Mardivirus Infection and Persistence in Feathers of a Chicken Model Harboring a Local Autoimmune Response

“…We observed some feather samplings with no detectable HVT genomes at some time points. We reported similar results earlier [ 10 ]. A chicken has more than 20,000 feathers and DNA was extracted from only two to three feathers at each sampling.…”

“…The HVT loads in feathers of SL and BL were moderate, rarely exceeding 10 4 HVT genome copies per million cells, with medians of 774 and 425, respectively. These viral loads were in accordance with the ones we reported in feathers in four different lines vaccinated at hatch with the same HVT-ND vaccine [ 10 ]. These viral loads were also similar to the ones reported by others in feathers of birds vaccinated with classical HVT vaccines in the first weeks post-vaccination, independent of the presence or absence of maternal antibodies against MDV [ 11 , 31 ].…”

“…It is important to question whether HVT genome copies measured in feathers are associated with HVT replication and/or correspond to the presence of latently infected T cells. In a previous theoretical calculation for a normal chicken, we estimated that 20 copies per million pulp cells may come from latently infected CD4+ T cells [ 10 ]. As feather tip material collected contained both feather pulp and epithelium, we can further reduce this number to about 10 copies per million feather cells possibly associated to latently infected CD4+ T cells.…”

“…All protocols were previously described [ 10 ]. Briefly, feather epithelium and pulp were collected mechanically by pressing and rubbing a scalpel blade on the sheaths of GF tips.…”

“…HVT appears to establish latency mostly in spleen cells, in which the HVT genome integrates into host chromosomes [ 9 ]. In the skin, HVT infection persists for weeks in feathers [ 10 ]. In this tissue, HVT infection is considered productive like MDV, based on viral shedding, evidenced by the presence of virus genome on the surface of the skin, in dander, and poultry dust [ 11 , 12 , 13 ].…”