Changing the neighbours: how herpesviruses modify surrounding cells

In cancer, abnormal cells grow uncontrollably. More than 15% of human cancers are a result of cancer-causing viruses, with greater prevalence in developing countries. Vaccines or antiviral drugs against cancer-causing viruses can prevent or treat cancer. For example, remarkably effective human papilloma virus (HPV) vaccines are already reducing the incidence of HPV-associated cervical cancer.

Kaposi’s sarcoma herpesvirus (KSHV) is a virus that causes cancer in people with suppressed immune systems, most notably including people with AIDS. KSHV stores its genetic information in DNA, but also relies on short segments of ribonucleic acid (RNA), called microRNAs, to help with infection. Normally, RNA serves as a ‘messenger’ that allows genetic sequences encoded in our DNA to be converted into proteins that perform a variety of tasks. For KSHV, these microRNAs don’t actually make proteins, but instead act as ‘dimmer switches’ that control production levels for specific viral and human cell proteins.

KSHV infection of a human cell causes a variety of changes to cell processes that are thought to promote cancer. Yogev et al. showed that when KSHV is dormant, meaning the viral genome is carried passively in the infected cell, KSHV can also influence processes in neighbouring

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Modified image from Yogev et al. article

uninfected cells. To do so, KSHV causes infected cells to release microRNA-containing packages that transfer the microRNAs to nearby cells. Once these bystander cells receive the packages, the viral microRNAs are released into the cell interior and initiate their ‘dimmer switch’ function on cellular genes. Ultimately, these viral microRNAs supercharge the metabolism of the cell, making it simultaneously more ‘cancer-like’ and better able to support future cycles of viral replication. Thus, Yogev et al. have discovered a new way that a virus can ‘pave the way’ for more efficient infection and disease.

Currently, KSHV infection does not have an effective treatment, but, Yogev et al. have demonstrated that viral microRNAs may serve as future therapeutic targets.

Summary written by: Emma Finlayson-Trick

To read the full paper, please click the following link:

Herpesviruses shape tumour microenvironment through exosomal transfer of viral microRNAs

Ohad Yogev, Stephen Henderson, Matthew John Hayes, Sara Sofia Marelli, Yifat Ofir-Birin, Neta Regev-Rudzki, Javier Herrero, Tariq Enver

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