Simultaneously Infecting White Blood Cells With Herpesvirus

The blood cancer can be simulating in the lab only by simultaneously infecting white blood cells; with two viruses typically found in the tumors. The successful creation of stable, cancer like cells in the lab opens up opportunities for understanding the progression of this and related cancers and, perhaps, developing treatments. Primary effusion lymphoma, PEL, is a rare blood cancer that primarily affects those with compromised immune systems, such as people infected with HIV.

The cancerous B cells that make up PEL nearly always harbor two viruses, Epstein-Barr Virus, or EBV, and Kaposi’s sarcoma associated herpesvirus, or KSHV; which are both known to induce other types of cancer. Previous research has largely failed to stably infect B cells with both viruses in the lab, the key to developing a productive model of the cancer for further research. When healthy B cells are exposed to both viruses within a day of one another, a small fraction of the cells remains infected for months.

White blood cells with herpesvirus

The researchers discovered a rare population of EBV and KSHV infected cells that outcompeted other cells in the lab; behaving much like cells from PEL tumors. This population of quickly growing cells will help researchers untangle how this rare cancer forms in the body; and how viruses can trigger cells to grow uncontrollably.

Lymphoma possibly arise from infection of two tumor viruses; and what are those two viruses contributing a member of the McArdle Laboratory for Cancer Research at the UW-Madison School of Medicine and Public Health. PEL-like behavior in B cells by infecting them with KSHV, the principal marker of the cancer. But those infections failed. Cells would slough off KSHV after days or weeks and did not continue to grow.

Fraction of B cells

Because EBV infection also strongly activates B cells, Faure and Sugden reasoned the virus might promote infection by KSHV. So Faure introduced both viruses to the cells, staggering infection by one or more days. EBV greatly increasing the fraction of B cells that were infecting with KSHV; although it was still limiting to about 2% of the original population.

Most importantly, EBV allowed the cells to grow and maintain the KSHV virus stably for months. Faure found that KSHV infection was most successful; when cells were infecting with EBV one day before being exposing to KSHV. That narrow window for success is likely one reason that dual infection; and subsequent development into PEL is rare in people. That community resource will drive a better understanding of how these viruses manipulate cells to form a lethal cancer.