Kaposi’s sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8 [HHV-8]) is a recently discovered member of this subfamily (23, 36), which has attracted much research activity on account of its involvement in the etiology of Kaposi’s sarcoma, a cancer prevalent in immunosuppressed AIDS patients (1, 16, 21, 25, 27, 38). Kaposi’s sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus associated with AIDS-associated Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD) [1]. Vero cell infection was confirmed through microscopic observation of viral cytopathic effect and classical herpesvirus syncytium formation. (MHC). Importantly, little is known about the regulation of gammaherpesvirus infection by IRF-1. 171:886-892, 2003). Ecology of the murine alphaherpesvirus and its isolation from lungs of rodents in cell culture.

doi:10.1128/mBio.01670-14. Like EBV (16, 21, 24) and KSHV (17, 20), γHV68 also latently infects other leukocytes, including macrophages (34) and dendritic cells (3), but the role that the macrophage and dendritic cell latency reservoirs play in the maintenance of chronic infection and viral pathogenesis is not yet understood. Murine gammaherpesvirus 68 (MHV68) is closely related to EBV and KSHV. Until recently, structural data for the tegument were limited to images from electron microscopy (EM) that suggested that the layer was comprised of an amorphous collection of proteins; however, more recent studies with human cytomegalovirus (HCMV) (29), herpes simplex virus 1 (HSV-1) (30, 31), murine gammaherpesvirus 68 (MHV-68) (32), RRV (33), and KSHV (34) indicate the presence of ordered tegument structures (30). Similarly to the EBV and rLCV miRNAs, the KSHV and RRV miRNAs are found at homologous genomic locations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Furthermore, the human herpesviruses carry genes that inhibit IFN-α/β action (46, 55, 58), and a subset of these genes is expressed during viral latency (9, 31, 65, 102), suggesting that IFN-α/β continues to exert antiviral effects after latency is established.

The RTA transcript contains two exons, with the first exon (amino acids [aa] 1 to 12) overlapping with the 3′ end of the ORF49 gene locus and the second (aa 13 to 571) mainly encoded by ORF50 (25, 41). Understanding how these viruses orient their tropism is therefore essential for the development of efficient antiviral strategies and approaches to control the consequences of these infections. However, even viruses with large genomes, such as the herpesviruses, require cellular proteins to supply activities not encoded in the viral genome. LANA was originally identified as a correlate of KSHV infection in AIDS-related Kaposi sarcoma (KS) lesions, as sera from patients with KS contained antibodies to LANA (6). These cells are sessile and capture antigens from the afferent lymph rather than from peripheral tissues. EBV and KSHV genomes exist as episomes during latency with production of linear genomes packaged in capsid proteins as a result of lytic activation (Decker et al., 1996; Knipe and Howley, 2013). KSHV is a member of the Gammaherpesvirinae subfamily of herpesviruses, which is comprised of lymphotropic tumor viruses including Epstein-Barr virus (EBV) and a mouse homolog of KSHV, murine herpesvirus 68 (MHV68, also known as murid herpesvirus 4).

Assembly of the virus in nuclear viral factories and budding through the inner lamella of the nuclear membrane which has been modified by the insertion of herpes glycoproteins, throughout the Golgi and final release at the plasma membrane. Neuro2A (a murine neuroblastoma cell line), SH-SY5Y (a human neuroblastoma cell line), BHK21 (a baby hamster kidney fibroblast cell line), and Vero (a green monkey kidney epithelial cell line) cells were propagated in complete Dulbecco’s modified Eagle’s medium supplemented with 10% fetal bovine serum and penicillin and streptomycin (10 units/ml) (HyClone). Epstein-Barr virus, first isolated from Burkitt’s lymphoma, has been detected in several malignant tumors originating in both lymphoid and epithelial tissues (1). Our results may provide a novel system to study persistent infection of γHVs in vitro and suggest a potential usage of MHV-68 as a gene delivery vector to the brain. Most differentially expressed genes were involved in immune signaling, immune response, or cell cycle pathways and many were associated with IFNg signaling. HDAC1 and 2 are metalloenzymes that share 83% sequence similarity and are frequently found in the same protein complex that is generally associated with transcriptional repression, such as the NuRD and CoREST. In the absence of an IFNγ response in vivo, persistent MHV68 replication emerges several weeks after infection and promotes a lethal inflammatory disorder consisting of lymphocytic infiltrates in multiple organs and fibrotic changes in the spleen, lymph nodes, and lung (6, 9).

This is an important gap in our knowledge, since viral transmission depends on lytic gene expression, and without understanding transmission, it is difficult to develop optimal strategies of infection control. Such is the case in early onset posttransplant lymphomas that are uniformly associated with EBV (71).