Viral RNAs Outwit the Immune System

Viral RNAs Outwit the Immune System

Herpes viruses are pathogenic DNA viruses known for establishing long-term latent infections. Some forms of herpes are sexually transmitted diseases and lead to genital lesions. Others are known for leading to “fever blisters” around the lips. Once the virus infects the cell, its viral genome is transcribed into viral mRNA and other smaller RNA molecules, collectively known as noncoding RNA or ncRNA. Some of the ncRNAs are very small, micro RNAs, while others are longer at about 100 nucleotides.

Researchers studying a herpes virus called human cytomega-lovirus (HCMV) recently showed that one of the functions of the longer ncRNA from the virus was to allow the infected cells to evade the innate immunity response, as shown in the figure. RNAs make excellent weapons against the immune system. They are fast-acting because they do not need to be translated, and they are poor targets for the adaptive immune response. 

HCMV is a herpes virus that causes severe disease in newborn infants and immunocompromised individuals. It encodes at least 2 long ncRNAs and 11 miRNAs. Current research suggests that these two ncRNAs are immune-response inhibitors.

Within hours of HCMV infection, a 2.7-kb viral ncRNA (2.7) accumulates, reaching 20% of the total viral RNA. This RNA binds to components of the mitochondrial respiratory chain complex I (MRCC-I), stabilizing its function as a countermeasure to apoptosis. Thus, b2.7 prevents the premature death of the infected cell and the steady production of ATP during the viral life cycle. The virus also produces a miRNA, miR-UL112. This miRNA inhibits the production of mRNA for a cell surface ligand that attracts natural killer cells. Thus, these two RNA molecules inhibit the destruction of the cell by NK cells as well as promoting the general strength of the host cell to prevent cell death.