The alphaherpesvirus pseudorabies virus (PrV) establishes latency primarily in neurons of trigeminal ganglia when only the transcription of the latency-associated transcript (LAT) locus is detected. Eleven microRNAs (miRNAs) cluster within the LAT, suggesting a role in establishment and/or maintenance of latency. We generated a mutant (M) PrV deleted of nine miRNA genes which displayed properties that were almost identical to those of the parental PrV wild type (WT) during propagation in vitro.
IMPORTANCEThis study provides a thorough reference on the establishment of latency by PrV in its natural host, the pig. Our results corroborate the evidence obtained from the study of several LAT mutants of other alphaherpesviruses encoding miRNAs from their LAT regions. Neither PrV miRNA expression nor high LLT expression levels are essential to achieve latency in trigeminal ganglia. Once latency is established by PrV, the only remarkable differences are found in the pattern of host response. This indicates that, as in herpes simplex virus, LAT functions as an immune evasion locus. P seudorabies virus (PrV) is a porcine alphaherpesvirus. The genome of PrV is more than 142 kb in size and is characterized by the presence of 70 different coding genes plus the latency-associated transcript (LAT) locus (1, 2). PrV is the etiological agent of Aujeszky's disease, causing neurological, respiratory, and reproductive disease in the pig, its natural host. Despite successful vaccination campaigns and eradication of the virus from various countries, pseudorabies outbreaks still occur in swine populations worldwide, as recently reported from China (3). Because latent infection persists for lifetime after recovery from acute disease, pigs latently infected by PrV are a constant danger for virus reactivation, shedding, and spread in susceptible populations (4-6).A particular feature of herpesviruses is their ability to establish and maintain latent infections in which the virus genome circularizes and persists as an episome. As for other alphaherpesviruses, neurons in the trigeminal ganglia are the primary site of PrV latency (7). Over this period, transcription of viral lytic genes is repressed and transcription of the viral genome is restricted to the LAT locus overlapping the internal repeat sequence (IR) (8-10).RNAs of multiple sizes are transcribed from the strand opposite that encoding EP0 and IE180, which can be detected in infected Citation Mahjoub N, Dhorne-Pollet S, Fuchs W, Endale Ahanda M-L, Lange E, Klupp B, Arya A, Loveland JE, Lefevre F, Mettenleiter TC, Giuffra E. 2015. A 2.5-kilobase deletion containing a cluster of nine microRNAs in the latencyassociated-transcript locus of the pseudorabies virus affects the host response of porcine trigeminal ganglia during established latency.