Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal

Bianca Schulte, Cindy Buffone, Silvana Opp, Francesca Di Nunzio, Daniel Augusto De Souza Aranha Vieira, Alberto Brandariz-Nuñez, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The interferon alpha (IFN-α)-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Fate-of-capsid experiments have correlated the ability of MxB to block HIV-1 infection with stabilization of viral cores during infection. We previously demonstrated that HIV-1 restriction by MxB requires capsid binding and oligomerization. Deletion and gain-of-function experiments have mapped the HIV-1 restriction ability of MxB to its N-terminal 25 amino acids. This report reveals that the N-terminal 25 amino acids of MxB exhibit two separate functions: (i) the ability of MxB to bind to HIV-1 capsid and (ii) the nuclear localization signal of MxB, which is important for the ability of MxB to shuttle into the nucleus. To understand whether MxB restriction of HIV-1 requires capsid binding and/or nuclear localization, we genetically separated these two functions and evaluated their contributions to restriction. Our experiments demonstrated that the <sup>11</sup>RRR<sup>13</sup> motif is important for the ability of MxB to bind capsid and to restrict HIV-1 infection. These experiments suggested that capsid binding is necessary for the ability of MxB to block HIV-1 infection. Separately from the capsid binding function of MxB, we found that residues <sup>20</sup>KY<sup>21</sup> regulate the ability of the N-terminal 25 amino acids of MxB to function as a nuclear localization signal; however, the ability of the N-terminal 25 amino acids to function as a nuclear localization signal was not required for restriction.

Original languageEnglish (US)
Pages (from-to)8599-8610
Number of pages12
JournalJournal of Virology
Volume89
Issue number16
DOIs
StatePublished - 2015

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Nuclear Localization Signals
nuclear localization signals
capsid
Capsid
Human immunodeficiency virus 1
HIV-1
HIV Infections
Amino Acids
amino acids
infection
interferon-alpha
reverse transcription
Interferon-alpha
Reverse Transcription
Infection

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal. / Schulte, Bianca; Buffone, Cindy; Opp, Silvana; Di Nunzio, Francesca; De Souza Aranha Vieira, Daniel Augusto; Brandariz-Nuñez, Alberto; Diaz-Griffero, Felipe.

In: Journal of Virology, Vol. 89, No. 16, 2015, p. 8599-8610.

Research output: Contribution to journalArticle

Schulte, B, Buffone, C, Opp, S, Di Nunzio, F, De Souza Aranha Vieira, DA, Brandariz-Nuñez, A & Diaz-Griffero, F 2015, 'Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal', Journal of Virology, vol. 89, no. 16, pp. 8599-8610. https://doi.org/10.1128/JVI.00753-15
Schulte B, Buffone C, Opp S, Di Nunzio F, De Souza Aranha Vieira DA, Brandariz-Nuñez A et al. Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal. Journal of Virology. 2015;89(16):8599-8610. https://doi.org/10.1128/JVI.00753-15
Schulte, Bianca ; Buffone, Cindy ; Opp, Silvana ; Di Nunzio, Francesca ; De Souza Aranha Vieira, Daniel Augusto ; Brandariz-Nuñez, Alberto ; Diaz-Griffero, Felipe. / Restriction of HIV-1 requires the N-terminal region of MxB as a capsid-binding motif but not as a nuclear localization signal. In: Journal of Virology. 2015 ; Vol. 89, No. 16. pp. 8599-8610.
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