Abstract
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-causing virus in humans, primarily affecting AIDS patients. KSHV causes a range of cancers including Kaposi’s sarcoma, pleural effusion lymphoma and multicentric Castleman’s disease. Current methods available for treating these cancers are relatively ineffective, and new targets for therapy are needed. The KSHV viral homolog of interleukin-6 gene (vIL-6) may play a significant role in tumor development and may serve as a new anti-cancer target, but its role in tumor formation is only partially understood. Here, a novel animal model was used to study how vIL-6 affects tumor development. Highly immune-deficient Rag2-/-γc-/- mice were transplanted with an immortalized human B cell line (BJAB) harboring either wild-type (WT) KSHV or a mutant strain lacking vIL-6 ΔvIL-6). Solid tumors developed and total tumor mass and the number of tumors were characterized. The vIL-6 gene had no significant impact on tumor mass, but significantly more tumors were detected when vIL-6 was present. Significant differences in expression of B cell markers in cells from extracted tumors were detected based upon the presence of vIL-6. B cell markers in tumor cells were also compared to the same cell type in culture, prior to xenotransplantation; B cell markers were mostly downregulated during tumor formation and these changes did not differ based upon the presence of vIL-6. The only marker that significantly increased in expression during tumor development was CD30. Tumor blood vessels were quantified to determine if more angiogenesis occurred with vIL-6-expressing virus, but there was no significant difference. These data indicate that vIL-6 plays a role in KSHV tumor formation in B cells in vivo. Further investigation into how vIL-6 manipulates CD30 expression may shed insight into KSHV oncogenesis, and may identify how vIL-6 can be targeted.
Highlights
Kaposi’s sarcoma herpesvirus (KSHV), known as human herpesvirus 8, is a gammaherpesvirus associated with multiple types of cancers in highly immunocompromised individuals [1]
There was no significant difference was detected in the mean tumor mass in animals injected with cells containing either WT KSHV (1.00g) or the ΔvIL-6 mutant (1.23g; p = 0.36; see Fig 1A)
When the Mean fluorescence intensity (MFI) was analyzed for each of these markers (Fig 5C), we found that many cellular populations were in accordance between the percentage of cells positive for the marker changing along with the MFI (e.g., CD45+, GFP+, CD19+, CD20+ all decreased by both parameters during tumor formation)
Summary
Kaposi’s sarcoma herpesvirus (KSHV), known as human herpesvirus 8, is a gammaherpesvirus associated with multiple types of cancers in highly immunocompromised individuals [1]. KSHV infects B cells and is associated with persistent infections which can lead to lymphoma, especially in AIDS patients. Besides KS, KSHV is thought to play a role in the development of B cell cancers such as primary effusion lymphoma (PEL) and Multicentric Castleman’s disease (MCD) [3]. Treatments for these cancers typically involve the use of monoclonal antibodies to target B cells for destruction, but the treatment targets noncancerous B cells [4]. Since patient prognosis is typically poor for these cancers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
