Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (KSHV) upregulates survivin expression in KSHV-Associated B-lymphoma cells and contributes to their proliferation
Authors: Pankaj Kumar
Subhash C Verma
Bingyi Xiao
Jie Lu
Erle S Robertson
Qiliang Cai
Masanao Murakami
Journal: Journal of Virology (2009)
Discipline: MICROBIOLOGY
Keywords: Survivin; LANA; KSHV; proliferation; gene arrays
Affiliations: Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Abstract:  Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpesvirus (KSHV) that is found in Kaposi's sarcoma tumors, upregulates survivin expression and increases the proliferation of KSHV-infected B cells. Analysis of pathway-specific gene arrays showed that survivin expression was highly upregulated in BJAB cells expressing LANA. The mRNA levels of survivin were also upregulated in HEK 293 and BJAB cells expressing LANA. Similarly, protein levels of survivin were significantly higher in LANA-expressing, as well as KSHV-infected, cells. Survivin promoter activity assays identified GC/Sp1 and p53 cis-acting elements within the core promoter region as being important for LANA activity. Gel mobility shift assays revealed that LANA forms a complex with Sp1 or Sp1-like proteins bound to the GC/Sp1 box of the survivin promoter. In addition, a LANA/p53 complex bound to the p53 cis-acting element within the survivin promoter, indicating that upregulation of survivin expression can also occur through suppression of p53 function. Furthermore, immunohistochemistry analyses revealed that survivin expression was upregulated in KSHV-associated Kaposi's sarcoma tissue, suggesting that LANA plays an important role in the upregulation of survivin expression in KSHV-infected endothelial cells. Knockdown of survivin expression by lentivirus-delivered small hairpin RNA resulted in loss of cell proliferation in KSHV-infected cells. Therefore, upregulation of survivin expression in KSHV-associated human cells contributes to their proliferation. 

Retracted: No

PubPeer comments:
 Figure 4. The first two lanes in the WB:myc blots (red arrows) and in the WB:GAPDH blots (blue arrows) appear to look similar across Figures 4 A through D; yet the third and fourth lanes look different. One could argue that the first two lanes show the same experiment across the four figure panels, but the photos are presented as single, unspliced blots. This suggests that photos have been spliced to make them look like a single blot. This splicing of blot photos makes it hard to compare sizes and exposure times of the bands. Could the authors please comment? ![file] , 
 Correction, July 2021: https: journals.asm.org doi 10.1128 JVI.00761-21  Fig. 4A to D: For the luciferase assay with results shown in the figure, the protein levels (WB:myc and WB:GAPDH) in the control lanes, pGL3B (empty vector), and the survivin promoter (SurP) are reshown in panels A through D. All of these lanes were derived from the same original blots and are reshown for easier comparison with the corresponding luciferase levels. I thank the authors and journal for clarifying this issue. ,