Heterogeneous Nuclear Ribonucleoprotein K Supports Vesicular Stomatitis Virus Replication by Regulating Cell Survival and Cellular Gene Expression

Abstract

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from infected cells. Further studies showed that hnRNP K suppresses apoptosis of virus-infected cells, resulting in increased cell survival during VSV infection. The increased survival of the infected cells was found to be due to the suppression of proapoptotic proteins such as Bcl-X S and Bik in a cell-type-dependent manner. Additionally, depletion of hnRNP K resulted in not only significantly increased levels of T-cell-restricted intracellular antigen 1 (TIA1) but also switching of the expression of the two isoforms of the protein (TIA1a and TIA1b), both of which inhibited VSV replication. hnRNP K was also found to support expression of several cellular proteins known to be required for VSV infection. Overall, our studies demonstrate hnRNP K to be a multifunctional protein that supports VSV infection via its role(s) in suppressing apoptosis of infected cells, inhibiting the expression of antiviral proteins, and maintaining the expression of proteins required for the virus.

hnRNP K Coordinates Transcriptional Silencing by SETDB1 in Embryonic Stem Cells

“…) may coincide with induction of the apoptotic pathway. Although hnRNP K regulates the expression of pro-apoptotic genes Bcl-Xs and Bik under certain conditions [ 44 ], these genes were not upregulated in hnRNP K KD mESCs. Nevertheless, Btg2 , Anxa8 , Perp , Trp73 , Cdkn1a and Casp14 were among the 16 apoptosis-associated genes identified by GO analysis.…”

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development

“…hnRNP A1 participates the reproduction of HIV, [539][540][541]563 HPV, [503][504][505] HCV, 471 EV-A71 472 and HTLV-1. 562 Inhibition of hnRNP C suppresses the replication of HCV, 438 poliovirus, 447,448 DENV, [479][480][481][482] EBV, 501 and HIV. 557,558 hnRNP D is required for HCV [452][453][454] and HIV 548,556 replication.…”

Type 1 diabetes cadaveric human pancreata exhibit a unique exocrine tissue proteomic profile

“…HNRNPK also plays key roles in regulating viral replication, e.g., Hepatitis C virus (HCV) , Hepatitis B virus , Vesicular stomatitis virus , Dengue virus type 2, and Junin virus . Virus replication is greatly increased by host expression of HNRNPK.…”