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YTHDF2 protein could help prevent viral infections associated with cancer

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The human herpes virus 8 – also termed Kaposi’s sarcoma-associated herpesvirus (KSHV) – is known to cause Kaposi sarcoma, which creates lesions in soft tissue (this includes the skin, oral cavity, lymph nodes and internal organs).

In a study published in Nature Microbiology, researchers from the Keck School of Medicine at the University of Southern California (USC; CA, USA) looked at particular modifications to mRNAs in order to observe KSHV infection.

Senior author of the study, Shou-Jiang Gao (USC), commented: “Understanding how the herpes virus switches from being dormant to causing cancer is important because of the health problems the herpes virus causes worldwide.”

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According to the WHO, 67% of the population are infected with two common types of herpes: genital herpes and cold sores. Most herpes viruses remain dormant until the host’s immune system weakens and when this occurs, some of these viruses are able to cause cancer.

In the study, scientists looked at mRNA modifications including N6-methyladenosine (m6A) and N6,2′-O-dimethyladenosine (m6Am) modifications (m6A/m). Within their study, the researchers stated that, “KSHV transcripts contain abundant m6A/m modifications during latent and lytic replication and these modifications are highly conserved among different cell types and infection systems.”

By mapping proteins that are able to restrict viral infections, the researchers found a protein termed YTHDF2 that can help regulate KSHV by detecting the m6A modification on viral mRNA. The protein is believed to be the key switch that regulates KSHV. When the team knocked down YTHDF2, they discovered that this enhanced viral replication by preventing KSHV RNA degradation.

Thus, the researchers believe that these results reveal a critical role of m6A/m modifications in the KSHV lifecycle and provide rich resources for future investigations.

“How the virus infects and replicates has a direct influence on how the cell becomes a cancer cell,” Gao explained, adding that you cannot cure cancer without some kind of a roadmap: “If a person has a disease and the problem area is in the hand, you wouldn’t want to treat the head. That’s why you need to map the disease pathway. In this case, the YTHDF2 protein detects the m6A modifications on mRNAs.”

“The findings from this study can potentially be translated into novel therapeutic approaches for cancers that are caused by viral infections,” concluded Gao.

Source: Tan B, Liu H, Zhang S et al. Viral and cellular N6-methyladenosine and N62’-O-dimethyladenosine epitranscriptomes in the KSHV life cycle. Nat. Microbiol. doi:10.1038/s41564-017-0056-8 (2017) (Epub ahead of print); USC press release  

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