Biology Reference
In-Depth Information
Latent Versus Lytic Infection
The finding that, with the exception of HCMV, all human herpesvirus miRNAs
originate from regions of the viral genome that are transcriptionally active during
latency suggests a role for herpesvirus miRNAs in latency. Indeed, recent data sug-
gest that miRNAs are potentially responsible for maintenance of a latent HSV-1
infection (Gupta et al. 2006). The HSV-1 mir-LAT has been shown to inhibit apop-
tosis in infected neuronal cells. However, as mir-LAT has not been shown to be
expressed during latency, its role in latent infection has yet to be proven.
As mentioned above, there is no simple tissue-culture model in which to study
HCMV latency. As such, there are no widely accepted HCMV gene products
known to contribute to the establishment and/or maintenance of a latent infection.
However, a promising recent cell culture model in which to study HCMV latency
has been reported recently(Goodrum et al. 2007). We hope that this will allow
future study of a potential role for HCMV miRNAs in latent infection.
Gammaherpesviruses, EBV and KSHV, establish latent infection in B cells.
Both can be induced to undergo lytic infection after treatment of infected cells with
either TPA or n-butyrate. The expression of EBV and KSHV miRNAs in latent vs
lytically infected cells has been studied in such systems.
For KSHV, there was little change in the expression of miRNAs after the switch
to lytic infection (Pfeffer et al. 2004, 2005; Cai et al. 2005). The exception from these
studies appears to be mir-K12-10, which showed an increase after induction of lytic
infection. Mir-K12-10 is located in the 3′-UTR of K12 (Cai et al. 2005; Pfeffer et al.
2005). K12 mRNA expression is increased during lytic infection and thus increased
levels of mir-K12-10 are consistent with upregulated expression of K12 mRNA. As
mir-K12-10 is the only KSHV miRNA not located in the intron (see Sect. 3.3 above),
it is interesting to speculate about whether mir-K12-10's location in the 3′ UTR of
K12 and its coincident expression are important to lytic replication.
Potential Function of HCMV miRNAs
Currently, miRNA target prediction lags far behind miRNA identification. As such,
just two of the 80 or so viral miRNAs in the miRNA registry have validated targets.
Simian Virus 40 (SV40), a polyomavirus, encodes one identified pre-miRNA that
yields mature miRNA(s) from each arm of the hairpin (Sullivan et al. 2005). These
miRNAs are perfectly complementary to early viral mRNAs and mediate cleavage
of transcripts leading to a decrease in viral T antigens (Sullivan et al. 2005). Ganem
and co-workers used a mutant virus deficient in the ability to form a pre-miRNA to
demonstrate viral miRNA function. Thus, the differential contribution of each arm
was not established and we refer to it as a single miRNA with a single function.
Interestingly, mutant virus lacking functional miRNAs showed no replicative
impairment in vitro and grew to wild type levels (Sullivan et al. 2005). Cells
infected with these mutant virus were, however, more susceptible to lysis by
