Nucleolin Interacts with US11 Protein of Herpes Simplex Virus 1 and Is Involved in Its Trafficking

Abstract

Herpes simplex virus type 1 (HSV-1) infection induces profound nucleolar modifications at the functional and organizational levels, including nucleolar invasion by several viral proteins. One of these proteins is US11, which exhibits several different functions and displays both cytoplasmic localization and clear nucleolar localization very similar to that of the major multifunctional nucleolar protein nucleolin. To determine whether US11 interacts with nucleolin, we purified US11 protein partners by coimmunoprecipitations using a tagged protein, Flag-US11. From extracts of cells expressing Flag-US11 protein, we copurified a protein of about 100 kDa that was further identified as nucleolin. In vitro studies have demonstrated that nucleolin interacts with US11 and that the C-terminal domain of US11, which is required for US11 nucleolar accumulation, is sufficient for interaction with nucleolin. This association was confirmed in HSV-1-infected cells. We found an increase in the nucleolar accumulation of US11 in nucleolin-depleted cells, thereby revealing that nucleolin could play a role in US11 nucleocytoplasmic trafficking through one-way directional transport out of the nucleolus. Since nucleolin is required for HSV-1 nuclear egress, the interaction of US11 with nucleolin may participate in the outcome of infection.

The Herpes Simplex Virus 1 Us11 Protein Inhibits Autophagy through Its Interaction with the Protein Kinase PKR

“…Us11 shuttles between the nucleus and the cytoplasm (43), and infection by two herpesviruses, HCMV and murine cytomegalovirus, causes the sequestration of PKR in the nucleus (44,45). We observed that a similar relocalization occurs in HSV-1-infected cells and that this depends on Us11 expression (data not shown).…”

Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA

“…2A). Instead, this initial redistribution was most likely a consequence of the viral disruption of cellular nucleoli (32,33). At 6 hpi, we observed two distinct populations of 7134-infected cells: (i) cells with small replication compartments and diffuse IFI16 staining (Fig.…”

Nucleolin Interacts with the Dengue Virus Capsid Protein and Plays a Role in Formation of Infectious Virus Particles

“…It is tempting to speculate that NCL could play a similar role in the assembly of the viral nucleocapsid complex. Indeed, NCL has been shown to enhance the release and infectivity of HIV-1 and to be involved in trafficking and nuclear egress of herpesvirus nucleocapsids (49)(50)(51). NCL could act as a chaperone for DENV C, assisting in the assembly of stable nucleoprotein complexes and perhaps aiding in the transport of the nucleocapsid to sites of maturation and egress.…”

“…NCL colocalizes with hepatitis D virus delta antigen and interacts with herpes simplex virus 1 protein US11, cytomegalovirus UL44, white-spot syndrome virus VP15, influenza virus (H3N2) NS1, and the NS5B protein of hepatitis C virus. These interactions have been shown to mediate a number of different processes, including protein synthesis, RNA replication, release of virions, and trafficking of viral proteins (48)(49)(50)(51)(52)(53)(54). In addition, NCL has been shown to interact with the untranslated regions (UTR) of several other viruses, including tombusvirus, feline calicivirus, Norwalk virus, and poliovirus, where it may play roles in virus replication (55)(56)(57).…”