The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates

Abstract

A gene of the Epstein-Barr virus (EBV), BamHI-C fragment rightward reading frame 1 (BCRF1), codes viral interleukin-10 (vIL-10), which is a close homolog to human IL-10. EBV strain variations are known at EBV latent membrane protein 1 (LMP1), and the distinct forms of LMP1 have been identified. In order to further elucidate the variations of EBV strains, the BCRF1 (vIL-10) gene was analyzed using PCR-direct sequencing in African Burkitt's lymphoma (BL) cell lines Raji, P3HR-1, EB1 and Daudi, Japanese BL cell line Akata, lymphoblastoid cell line OB and 22 wild EBV isolates from eight gastric carcinoma tissues and 14 throat washes. We found only five variations of the vIL-10 gene in them with one silent mutation and three non-silent mutations. Raji had no mutation to the prototype gene of B95-8. EB1 and P3HR-1 had non-silent mutations in the sequences leading to the arginine/serine and threonine/proline interchanges at residues 4 and 166, respectively. The silent mutation was detected at valine 102 in Daudi and also in the Japanese cell lines Akata, OB and 20 (90.9%) of the wild EBV isolates. The type of variations in the vIL-10 gene had a common relationship with those in the LMP1 gene. All of the variants of valine 102 had China1-type LMP1 sequences except for Daudi with Med-type LMP1 and other minorities with B95-8 type LMP1. The conservativeness of vIL-10 with a few variations suggests the indispensability of the vIL-10 gene in EBV and that the variations of the vIL-10 gene may depend upon the geographical prevalence of the EBV strains. This is the first report regarding the variations of the vIL-10 gene in cell lines and other wild isolates.

Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

“…The overall conserved character of the BARF1 gene suggests the importance of BARF1 function for virus-driven immortalization and escape strategies in an epithelial context. This is in line with the low variability of other lytic cycle proteins, like the viral IL10 encoded in BCRF1 [48] and the major envelope protein gp350/220 encoded in BLLF1 [49]. The limited overall sequence diverged at the protein level in different EBV isolates suggests BARF1 to play an important role in epithelial persistence during natural viral infection in man.…”

Repeated TLR9 stimulation results in macrophage activation syndrome–like disease in mice

“…Our results also provide a possible explanation for the spectrum of severity of secondary MAS, in that IL-10 responsiveness can change the degree of pathology seen, including the presence of hemophagocytosis. Differences in IL-10 responsiveness could be due to host factors in polymorphisms of IL-10 or IL-10 receptor signaling machinery or in polymorphisms in viral IL-10 produced by MAS inducing viruses such as EBV (45).…”

The evolutionary biology of poxviruses

“…All four of these cytokines are involved in regulating immune responses; but their roles are complex and so far not completely elucidated (Commins et al 2008). The first viral IL-10 homolog to be discovered was in Human herpesvurus 4 (also known as Epstein-Barr virus or EBV), and this molecule is perhaps the best studied viral cytokine homolog (Kanai et al 2007). The IL-10 molecule of EBV acts together with host IL-10 to down-regulate the host immune response early in EBV infection of host B cells (Kanai et al 2007).…”