The C-terminal half of TSG101 blocks rous sarcoma virus budding and sequesters gag into unique nonendosomal structures

Marc C. Johnson, Jared L. Spidel, Danso Ako-Adjei, John W. Wills, Volker M. Vogt

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Retroviral late domains (L domains) are short amino acid sequences in the Gag protein that facilitate the process of budding. L domains act by recruiting the ESCRT complexes, which normally function in the formation of multivesicular bodies. The PTAP late domain of human immunodeficiency virus (HIV) is believed to specifically recruit this machinery by binding the ESCRT protein TSG101. It was recently demonstrated that expression of a C-terminal fragment of TSG101 (TSG-3′) blocked the budding of both PTAP-dependent and PPPY-dependent retroviruses. We show here that TSG-3′ expression leads to the formation of large spherical entities that we call TICS (TSG-3′-induced cellular structures) in the cytoplasm. Rous sarcoma virus (RSV) and murine leukemia virus (MLV) Gag proteins are selectively recruited to these structures, but HIV type 1 Gag is completely excluded. Experiments with various HIV and RSV vector constructs as well as HIV and RSV chimeras suggest that recruitment to the TICS is late domain independent and does not involve recognition of any single amino acid sequence. TICS appear to have no limiting membrane and do not colocalize with markers for any membranous cellular compartment. Wild-type TSG101 is also recruited to TICS, but most other ESCRT proteins are excluded. These structures are similar in nature to aggresomes, colocalize with the aggresome marker GFP-250, and are highly enriched in ubiquitin but in other ways do not fully meet the description of aggresomes. We conclude that the block to retroviral budding by TSG-3′ may be the result of its sequestration of Gag, depletion of free TSG101, or depletion of free ubiquitin.

Original languageEnglish (US)
Pages (from-to)3775-3786
Number of pages12
JournalJournal of virology
Volume79
Issue number6
DOIs
StatePublished - Mar 1 2005

Fingerprint

Rous sarcoma virus
Virus Release
cell structures
Cellular Structures
Human immunodeficiency virus
Endosomal Sorting Complexes Required for Transport
gag Gene Products
HIV
ubiquitin
Ubiquitin
Amino Acid Sequence
Retroviridae
amino acid sequences
Murine leukemia virus
Multivesicular Bodies
Murine Leukemia Viruses
proteins
chimerism
Human immunodeficiency virus 1
HIV-1

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Johnson, Marc C. ; Spidel, Jared L. ; Ako-Adjei, Danso ; Wills, John W. ; Vogt, Volker M. / The C-terminal half of TSG101 blocks rous sarcoma virus budding and sequesters gag into unique nonendosomal structures. In: Journal of virology. 2005 ; Vol. 79, No. 6. pp. 3775-3786.
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The C-terminal half of TSG101 blocks rous sarcoma virus budding and sequesters gag into unique nonendosomal structures. / Johnson, Marc C.; Spidel, Jared L.; Ako-Adjei, Danso; Wills, John W.; Vogt, Volker M.

In: Journal of virology, Vol. 79, No. 6, 01.03.2005, p. 3775-3786.

Research output: Contribution to journalArticle

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