Feline immunodeficiency virus gag is a nuclear shuttling protein

Iris Kemler, Dyana Saenz, Eric Poeschla

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Lentiviral genomic RNAs are encapsidated by the viral Gag protein during virion assembly. The intracellular location of the initial Gag-RNA interaction is unknown. We previously observed feline immunodeficiency virus (FIV) Gag accumulating at the nuclear envelope during live-cell imaging, which suggested that trafficking of human immunodeficiency virus type 1 (HIV-1) and FIV Gag may differ. Here we analyzed the nucleocytoplasmic transport properties of both Gag proteins. We discovered that inhibition of the CRM1 nuclear export pathway with leptomycin B causes FIV Gag but not HIV-1 Gag to accumulate in the nucleus. Virtually all FIV Gag rapidly became intranuclear when the CRM1 export pathway was blocked, implying that most if not all FIV Gag normally undergoes nuclear cycling. In FIV-infected feline cells, some intranuclear Gag was detected in the steady state without leptomycin B treatment. When expressed individually, the FIV matrix (MA), capsid (CA), and nucleocapsid-p2 (NC-p2) domains were not capable of mediating leptomycin B-sensitive nuclear export of a fluorescent protein. In contrast, CANC-p2 did mediate nuclear export, with MA being dispensable. We conclude that HIV-1 and FIV Gag differ strikingly in a key intracellular trafficking property. FIV Gag is a nuclear shuttling protein that utilizes the CRM1 nuclear export pathway, while HIV-1 Gag is excluded from the nucleus. These findings expand the spectrum of lentiviral Gag behaviors and raise the possibility that FIV genome encapsidation may initiate in the nucleus.

Original languageEnglish (US)
Pages (from-to)8402-8411
Number of pages10
JournalJournal of Virology
Volume86
Issue number16
DOIs
StatePublished - Aug 2012

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Feline Immunodeficiency Virus
Feline immunodeficiency virus
nuclear proteins
Nuclear Proteins
Cell Nucleus Active Transport
Human immunodeficiency virus 1
HIV-1
gag Gene Products
nucleocytoplasmic transport
RNA
Nucleocapsid
nucleocapsid
capsid
Capsid
viral proteins
Felidae
Nuclear Envelope
nuclear membrane
virion
Virion

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Feline immunodeficiency virus gag is a nuclear shuttling protein. / Kemler, Iris; Saenz, Dyana; Poeschla, Eric.

In: Journal of Virology, Vol. 86, No. 16, 08.2012, p. 8402-8411.

Research output: Contribution to journalArticle

Kemler, Iris ; Saenz, Dyana ; Poeschla, Eric. / Feline immunodeficiency virus gag is a nuclear shuttling protein. In: Journal of Virology. 2012 ; Vol. 86, No. 16. pp. 8402-8411.
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