LC Sciences News

MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in posttranscriptional regulation. miRNAs are utilized in organisms ranging from plants to higher mammals, and data have shown that DNA viruses also use this method for host and viral gene regulation.

Cytomegalovirus (CMV) infections are frequently associated with the salivary glands in humans and other mammals. Several species of CMV have been identified and classified for different mammals.  The most studied is human CMV (HCMV), however other primate CMV species include chimpanzee CMV (CCMV), simian CMV (SCCMV) and rhesus CMV (RhCMV) that infect macaques.

HCMV miRNAs are important for regulation of viral infection and evasion of host immune responses. Unfortunately, the importance of HCMV miRNAs cannot be addressed in vivo due to the species specificity of CMVs. Rhesus CMV (RhCMV) infection of rhesus macaques provides an important model system for HCMV pathogenesis due to the genetic similarity between the viruses.

In a recent study¹, a team led by researchers at the Vaccine and Gene Therapy Institute, Oregon Health & Sciences University used small RNA sequencing to discover that RhCMV encodes 13 miRNAs that are clustered in distinct regions of the viral genome and the miRNAs display unique patterns of expression in rhesus fibroblasts. They found that HCMV miRNAs are undetectable at very early times in infection but increase in abundance throughout infection. Examination of salivary gland tissue from infected animals revealed the presence of a subset of viral miRNAs suggesting there may be important roles for specific RhCMV miRNAs in the salivary gland during persistent infection. This study highlights the importance of the RhCMV model system for evaluating the roles of CMV miRNAs during viral infection.

In a previous study², another OSHU team sequenced the small RNAs in rat cytomegalovirus (RCMV)-infected fibroblasts and persistently infected salivary glands. They identified 24 unique miRNAs that mapped to hairpin structures found within the viral genome. The RCMV miRNAs have a genomic positional orientation similar to that of the miRNAs described for mouse cytomegalovirus, but they do not share any substantial sequence conservation. Interestingly, they found a number of specific examples of differential isoform usage between the fibroblast and salivary gland samples. Additionally, the researchers determined that viral miRNAs are expressed in most tissues during the acute infection phase. This study identified the miRNAs expressed by RCMV in vitro and in vivo and demonstrated that expression is tissue specific and associated with a stage of viral infection.

Together, these studies demonstrate small RNA sequencing as a powerful tool for the study of virus miRNAs and their roles in gene regulation during infection.

1. Hancock MH, Tirabassi RS, Nelson JA. (2012) Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo. Virology [Epub ahead of print]. [abstract]
2. Meyer C, Grey F, Kreklywich CN, Andoh TF, Tirabassi RS, Orloff SL, Streblow DN. (2010) Cytomegalovirus MicroRNA Expression Is Tissue Specific and Is Associated with Persistence. J Virol 85(1), 378-89. [article]