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Credit: Ed Uthman
New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.
It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.
This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.
Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.
The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.
Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.
To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.
The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.
When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.
The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.
“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.” 
Credit: Ed Uthman
New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.
It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.
This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.
Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.
The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.
Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.
To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.
The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.
When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.
The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.
“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.”
Credit: Ed Uthman
New research has revealed how Epstein Barr virus (EBV) and other herpes viruses outwit the body’s immune response.
It seems these viruses carry microRNAs (miRNAs) that block the interferon (IFN) response—when immune cells release IFN to prevent viral replication, which often kills or slows the growth of infected host cells.
This appears to explain why patients with EBV-positive lymphomas and other viral cancers may resist treatment with IFN.
Jennifer Cox, a graduate student at the University of Texas Austin, and her colleagues recounted these findings in PNAS.
The team noted that many viruses, including EBV, carry miRNAs they use to hijack natural processes in a host’s cells during an infection.
Viral miRNAs are known to prevent host cell death, promote host cell growth, and dampen the host cell’s viral defenses. However, scientists don’t yet know which viral miRNAs perform which functions.
To gain some insight, Cox and her colleagues screened a library of more than 70 human viral miRNAs. This revealed 3 unrelated miRNAs from distantly related herpes viruses that significantly inhibited IFN signaling.
The 5’ and 3’ derivatives from EBV-encoded miR-BART-18 precursor miRNA and the orthologous precursor miRNA from Rhesus lymphocryptovirus all reduced expression of the cyclic AMP-responsive element-binding protein (CBP), which, as part of the p300-CBP complex, mediates IFN signaling.
When the researchers restored miR-BART-18 to cells infected with an EBV miRNA mutant, they observed a cellular growth advantage upon IFN treatment. And they found that miRNAs from other herpes viruses were able to complement this activity.
The team also showed that blocking miR-BART-18 function in an EBV-positive tumor cell line rendered cells more susceptible to IFN-mediated effects.
“[These findings] could explain the variability seen in the success of previous interferon-based cancer treatments,” Cox said. “While this work does not immediately identify new drugs, the fact that such different tumor viruses have converged on the same strategy makes this an exciting pursuit for future therapies against viral cancers.”