Kaposi Sarcoma–Associated Herpesvirus Mimics Host Signal to Drive Cell Growth, Protein Production
In a study report published by Bhatt et al in Proceedings of the National Academy of Sciences, researchers at the University of North Carolina Lineberger Comprehensive Cancer Center explained how a type of herpesvirus uses mimicry to trick the host cell to produce proteins the virus needs and drive cell growth. The findings have implications for how the virus causes cancer.
The researchers explained that the Kaposi sarcoma–associated herpesvirus makes a protein called vPK, which shares a number of similarities to a host cell protein named S6KB1. The virus manipulates the S6KB1 host cell signaling pathway to spur the host cell to make more proteins and divide. The researchers said their findings shed light on a potential cancer-causing mechanism of the virus.
“Cancer is a multistep process, and to turn a normal cell into a cancer cell, a number of events need to occur,” said the study's senior author Blossom Damania, PhD, Co-Director of the UNC Lineberger Global Oncology Program and the UNC Lineberger Virology Program. “Some of those steps involve increasing cell proliferation, others involve preventing cell death, and yet others involve the cell evading host immunity. This process usually requires multiple events that target these different pathways before a cell becomes cancerous. We think that different viral proteins are targeting different cell pathways, and the one we identified in this study is targeting cell protein synthesis and cell growth.”
Kaposi sarcoma–associated herpesvirus is linked to several types of cancer, including Kaposi sarcoma and two types of lymphomas. People who have a weakened immune system, such as transplant recipients who take immunosuppressive drugs or those infected with human immunodeficiency virus (HIV), are at increased risk of developing Kaposi sarcoma when infected with the virus.
Previous studies have shown that Kaposi sarcoma–associated herpesvirus can make proteins that keep the host cells from triggering its own death or that prevent warning signals to the body’s defense system in response to the virus.
Study Findings
In their new study, the researchers used computer modeling to reveal the viral protein vPK is structurally similar to a host protein. They also used other biochemical and molecular methods to determine that the two proteins target similar signals in the cell.
Based on those and other findings, Dr. Damania and her colleagues concluded that the viral protein mimics the human protein’s function, causing the host cell to increase protein production, divide, and encourage angiogenesis. With such virally promoted functions relatively unchecked, the researchers believe those functions could contribute to the abnormal cell growth characteristic of cancer.
“This viral protein does not contain the same ‘checks’ that keep the cellular protein in line, so it can perform this function without being controlled by the brakes the cell normally uses to control activity of the cellular protein,” said Dr. Damania, who is also incoming Vice Dean for Research at the UNC School of Medicine and the Cary C. Boshamer Distinguished Professor of Microbiology and Immunology. “So, essentially, the viral protein can function unregulated and, hence, might contribute to the development of cancers associated with this virus by augmenting cell proliferation.”
These findings may also have implications for treatment of viral cancers.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
