{Reference Type}: Journal Article
{Title}: How Kaposi's sarcoma-associated herpesvirus stably transforms peripheral B cells towards lymphomagenesis.
{Author}: Faure A;Hayes M;Sugden B;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 116
{Issue}: 33
{Year}: 08 2019 13
{Factor}: 12.779
{DOI}: 10.1073/pnas.1905025116
{Abstract}: Primary effusion lymphomas (PELs) are causally associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and 86% of PELs are coinfected with Epstein-Barr virus (EBV). Understanding how PELs develop has been impaired by the difficulty of infecting B cells with KSHV in vitro, and the inability of KSHV to transform them. We show that EBV supports an optimal coinfection of 2.5% of peripheral B cells by KSHV. This coinfection requires 1 or more transforming genes of EBV but not entry into KSHV's lytic cycle. We demonstrate that dually infected B cells are stably transformed in vitro and show that while both viruses can be maintained, different cells exhibit distinct, transformed properties. Transformed cells that grow to predominate in a culture express increased levels of most KSHV genes and differentially express a subset of cellular genes, as do bona fide PEL cells. These dually infected peripheral B cells are thus both stably transformed and allow in vitro molecular dissection of early steps in the progression to lymphomagenesis.