Persistence of bovid herpesvirus-4 in experimentally inoculated pregnant rabbits

To study the persistence and reactivation of bovid herpesvirus-4 (BHV-4), pregnant rabbits were inoculated with BHV-4 via the intrauterine route. Disease production and virus shedding were monitored for up to 67 days post infection (DPI). Virus isolation was attempted from nasal, vaginal and buffy coat samples of all rabbits. Virus shedding was observed between 5 and 12 DPI but not thereafter. Some of the animals were given intramuscular injections of dexamethasone (DEX) for 4 consecutive days starting at 7 weeks post infection. One group of rabbits was euthanized at 5 days post-DEX treatment (58 DPI) and the other was euthanized 2 weeks post-DEX treatment (67 DPI). Virus shedding was not detected in either group but BHV-4 was recovered on multiple occasions from spleen, kidney, uterus, and ovary explants of both DEX-treated and non-treated rabbits indicating that BHV-4 can persist in these organs but cannot be reactivated by DEX. To further study the in vitro reactivation of persistent BHV-4, a methylating agent, hexamethylenebisacetamide (HMBA), was used in organ cultures of neural and extraneural tissues. Limited data on enhanced recovery of BHV-4 from spleen indicated that it may be the site of latency in BHV-4 infection.