Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

Shuichi Kusano; Yoshito Eizuru

doi:10.1016/j.bbrc.2013.02.098

Interaction of the phospholipid scramblase 1 with HIV-1 Tat results in the repression of Tat-dependent transcription

Biochem Biophys Res Commun. 2013 Apr 19;433(4):438-44. doi: 10.1016/j.bbrc.2013.02.098. Epub 2013 Mar 15.

Authors

Shuichi Kusano¹, Yoshito Eizuru

Affiliation

¹ Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. skusano@m2.kufm.kagoshima-u.ac.jp

PMID: 23501106
DOI: 10.1016/j.bbrc.2013.02.098

Abstract

Human phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)-stimulated gene and possesses an IFN-mediated antiviral function. We show here that PLSCR1 directly interacts with human immunodeficiency virus type-1 (HIV-1) Tat. This interaction occurs both in vitro and in vivo through amino acids 160-250 of PLSCR1. Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. In addition, shRNA-mediated suppression of endogenous PLSCR1 expression enhances the levels of gag mRNA in an HIV-1-infected T-cell line. These findings indicate that PLSCR1 negatively regulates the Tat-dependent transactivation of the HIV-1 LTR during HIV-1 infection.

MeSH terms

Animals
Binding Sites
COS Cells
Cell Nucleus / metabolism
Cell Nucleus / virology
Chlorocebus aethiops
Cytoplasm / metabolism
Cytoplasm / virology
Gene Expression Regulation
HIV Infections / metabolism
HIV Infections / pathology
HIV Infections / virology
HIV Long Terminal Repeat
HIV-1 / metabolism*
HIV-1 / pathogenicity
Host-Pathogen Interactions*
Humans
Phospholipid Transfer Proteins / genetics
Phospholipid Transfer Proteins / metabolism*
Protein Interaction Mapping
Protein Stability
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
T-Lymphocytes / virology
Transcription, Genetic*
Transcriptional Activation
Transfection
gag Gene Products, Human Immunodeficiency Virus / genetics
gag Gene Products, Human Immunodeficiency Virus / metabolism
tat Gene Products, Human Immunodeficiency Virus / genetics
tat Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

PLSCR1 protein, human
Phospholipid Transfer Proteins
RNA, Messenger
RNA, Small Interfering
gag Gene Products, Human Immunodeficiency Virus
tat Gene Products, Human Immunodeficiency Virus