Insights into the Roles of Cyclophilin A During Influenza Virus Infection

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection.

Related collections

Most cited references 52

Record: found
Abstract: found
Article: not found

Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade.

Stephan Pleschka, O Planz, G Hobom … (2001)

Influenza A viruses are important worldwide pathogens in humans and different animal species. The functions of most of the ten different viral proteins of this negative-strand RNA virus have been well elucidated. However, little is known about the virus-induced intracellular signalling events that support viral replication. The Raf/MEK/ERK cascade is the prototype of mitogen-activated protein (MAP) kinase cascades and has an important role in cell growth, differentiation and survival. Investigation of the function of this pathway has been facilitated by the identification of specific inhibitors such as U0126, which blocks the cascade at the level of MAPK/ERK kinase (MEK). Here we show that infection of cells with influenza A virus leads to biphasic activation of the Raf/MEK/ERK cascade. Inhibition of Raf signalling results in nuclear retention of viral ribonucleoprotein complexes (RNPs), impaired function of the nuclear-export protein (NEP/NS2) and concomitant inhibition of virus production. Thus, signalling through the mitogenic cascade seems to be essential for virus production and RNP export from the nucleus during the viral life cycle.

0 comments Cited 174 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells

Nicolas Manel, Brandon Hogstad, Yaming Wang … (2010)

Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses(1,2). Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known(3). DC are largely resistant to infection with HIV-1(4), but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement(5,6). We show here that, when DC resistance to infection is circumvented(7,8), HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine.

0 comments Cited 168 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Specific incorporation of cyclophilin A into HIV-1 virions.

E K Franke, H E Yuan, J Luban (1994)

Little is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl-prolyl isomerases; cyclophilins catalyse a rate-limiting step in protein folding and protect cells from heat shock. Here we demonstrate that cyclophilin A is specifically incorporated into HIV-1 virions but not into virions of other primate immunodeficiency viruses. A proline-rich region conserved in all HIV-1 Gag polyproteins is required for cyclophilin A binding and incorporation. Disruption of a single proline blocks the Gag-cyclophilin interaction in vitro, prevents cyclophilin A incorporation into virions, and inhibits HIV-1 replication. Our results indicate that the interaction of Gag with cyclophilin A is necessary for the formation of infectious HIV-1 virions.

0 comments Cited 141 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 15 January 2013

Publication date Collection: January 2013

Volume: 5

Issue: 1

Pages: 182-191

Affiliations

Center for Molecular Virology, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; E-Mails: xiaolingliu03@ 123456163.com (X.L.), mrzzdnew@ 123456163.com (Z.Z.)

Author notes

[* ] Author to whom correspondence should be addressed; E-Mail: liuwj@ 123456im.ac.cn ; Tel.: +86-10-64807497; Fax: +86-10-64807503.

Article

Publisher ID: viruses-05-00182

DOI: 10.3390/v5010182

PMC ID: 3564116

PubMed ID: 23322171

SO-VID: 21a3579b-c585-4151-b407-a88ed7d0f5a1

License:

This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

Insights into the Roles of Cyclophilin A During Influenza Virus Infection

Read this article at

Abstract

Related collections

MDPI: Coronavirus

Most cited references 52

Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade.

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells

Specific incorporation of cyclophilin A into HIV-1 virions.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 464

Cited by 13

Most referenced authors 779