Donofrio Gaetano, van Santen Vicky L
Istituto di Malattie Infettive Veterinarie, Facoltá di Medicina Veterinaria, Universita degli Studi di Parma, 43100 Parma, Italy1.
Department of Pathobiology, 264 Greene Hall, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5519, USA2.
J Gen Virol. 2001 May;82(Pt 5):1181-1185. doi: 10.1099/0022-1317-82-5-1181.
Although bovine herpesvirus-4 (BHV-4), a gammaherpesvirus lacking a clear disease association, has been demonstrated in many tissues during persistent BHV-4 infection, a likely site of virus persistence is in cells of the monocyte/macrophage lineage. To establish an in vitro model of persistent infection potentially useful for examining the molecular mechanisms of BHV-4 persistence/latency, we infected the bovine macrophage cell line BOMAC. Following extensive cell death, surviving cells were found to be persistently infected, maintaining the viral genome over many passages and producing low levels of infectious virus. Although selection was unnecessary for the maintenance of the viral genome, cells persistently infected with recombinant BHV-4 containing a neomycin-resistance gene could be selected with geneticin, thus confirming that persistent BHV-4 infection was compatible with cell survival and replication. Furthermore, persistent BHV-4 infection caused no decrease in the growth rate of BOMAC cells. Sodium butyrate, which reactivates latent gammaherpesviruses in vitro, or dexamethasone, which reactivates latent BHV-4 in vivo, increased viral DNA by 10- to 15-fold in persistently infected BOMAC cells. This suggests that reactivation of latent BHV-4 by dexamethasone in vivo might involve direct action of dexamethasone on latently infected cells.
虽然牛疱疹病毒4型（BHV - 4）是一种缺乏明确疾病关联的γ疱疹病毒，在BHV - 4持续感染期间已在许多组织中得到证实，但其可能的病毒持续存在位点是单核细胞/巨噬细胞谱系的细胞。为了建立一个可能有助于研究BHV - 4持续存在/潜伏分子机制的体外持续感染模型，我们感染了牛巨噬细胞系BOMAC。在大量细胞死亡后，发现存活的细胞被持续感染，在许多传代过程中维持病毒基因组并产生低水平的感染性病毒。虽然维持病毒基因组不需要选择，但用遗传霉素可以选择感染含有新霉素抗性基因的重组BHV - 4的持续感染细胞，从而证实BHV - 4持续感染与细胞存活和复制是相容的。此外，BHV - 4持续感染并未导致BOMAC细胞生长速率下降。在体外可重新激活潜伏γ疱疹病毒的丁酸钠或在体内可重新激活潜伏BHV - 4的地塞米松，使持续感染的BOMAC细胞中的病毒DNA增加10至15倍。这表明地塞米松在体内重新激活潜伏BHV - 4可能涉及地塞米松对潜伏感染细胞的直接作用。
