Rotavirus-encoded nonstructural protein 1 modulates cellular apoptotic machinery by targeting tumor suppressor protein p53
Authors: Rahul Bhowmick
Shiladitya Chattopadhyay
Mamta Chawla-Sarkar
Umesh Chandra Halder
Mukti Kant Nayak
Journal: Journal of Virology (2013)
Discipline: MICROBIOLOGY
Keywords: p53; rotaviruses; NSP1; apoptosis; degradation
Affiliations: Division of Virology, National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, India.

Abstract:  p53, a member of the innate immune system, is triggered under stress to induce cell growth arrest and apoptosis. Thus, p53 is an important target for viruses, as efficient infection depends on modulation of the host apoptotic machinery. This study focuses on how rotaviruses manipulate intricate p53 signaling for their advantage. Analysis of p53 expression revealed degradation of p53 during initial stages of rotavirus infection. However, in nonstructural protein-1 (NSP1) mutant strain A5-16, p53 degradation was not observed, suggesting a role of NSP1 in this process. This function of NSP1 was independent of its interferon or phosphatidylinositol 3-kinase (PI3K)/AKT modulation activity since p53 degradation was observed in Vero cells as well as in the presence of PI3K inhibitor. p53 transcript levels remained the same in SA11-infected cells (at 2 to 14 h postinfection), but p53 protein was stabilized only in the presence of MG132, suggesting a posttranslational process. NSP1 interacted with the DNA binding domain of p53, resulting in ubiquitination and proteasomal degradation of p53. Degradation of p53 during initial stages of infection inhibited apoptosis, as the proapoptotic genes PUMA and Bax were downregulated. During late viral infection, when progeny dissemination is the main objective, the NSP1-p53 interaction was diminished, resulting in restoration of the p53 level, with initiation of proapoptotic signaling ensuing. Overall results highlight the multiple strategies evolved by NSP1 to combat the host immune response. 

Retracted: No

PubPeer comments:
 Concern about Figure 3C and 3D: Some background dots appear to be visible in the NSP1 panels in both Figure 3C and 3D (shown in blue). Some other background spots appear to be visible twice in the NSP1 panel of Figure 3C (shown in red). ![file] , 
 #1 I agree. There may also be an issue with Figure 1B. Perhaps the authors could post the uncropped scans. *** ![file] , 
 Perhaps Figure 2A has mismatched number of lanes too? *** Enhanced brightness ![file] *** Original ![file] , 
 Correction, February 2021: https: journals.asm.org doi 10.1128 JVI.02302-20  Page 6841: In Fig. 1B (Vero cells infected with the RV-SA11 strain), the NSP1 0 hours postinfection (0 hpi) lane was cropped out by mistake. The corrected blot should appear as shown below.  Page 6842: In Fig. 2A (MA104 cells infected with the RV-A5-16 strain), the NSP1 panelu2019s mock infection data point was cropped out by mistake. The corrected blot should appear as shown below. Of note, both Figure 2A appears to have been replaced by other panels, suggesting this was not just a cropping error. Also of note, the potential repetitive patterns in Figure 3 have not been addressed in this correction. Could the authors please comment on those? ,