Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

Table 1

Summary of EBV gene products related to microRNA gene regulation. EBV gene products modulate levels of host-encoded factors shared with immune response regulatory factors such as NF-κB. Most EBV-encoded BART microRNAs are upregulated by NF-κB during viral latency and in turn increase stability of a large number of cellular transcripts that play a role in both resistance of cells to apoptosis and also evasion of the host immune response. EBV-encoded BZLF-1 protein (ZEBRA) downregulates NF-κB and promotes viral lytic growth and host cell apoptosis. Some BART which are homologues of host miR155 may counterregulate other BART and decrease NF-κB. ZEBRA-regulated factors may also upregulate other viral host gene products associated with genome instability (see text).

Transcript	+/−	Effects
BART (1, 2, 3...) microRNA (viral)	NF-κB	Resistance to apoptosis, immune surveillance, host genome instability
LMP2A protein	NF-κB	Resistance to apoptosis, immune surveillance, increased HERV expression
BZLF1 protein (ZEBRA)	NF-κB; AP-1; Sp1; CREB	Increased apoptosis, viral replication proteins, viral replication; Host genome instability?
BART5-5p miR155 (viral and host)	NF-κB?	Feedback regulation of BART, NF-κB?