Evidence for a second function of the MA sequence in the Rous sarcoma virus Gag protein

Parent, Leslie J.; Wilson, Carol; Resh, Marilyn D.; Wills, John W.

doi:10.1128/jvi.70.2.1016-1026.1996

Cited by 52 publications

(24 citation statements)

References 55 publications

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“…The low level of particle release exhibited by this mutant cannot explain the loss of infectivity, since the EP peptide restored infectivity despite further decreasing the budding efficiency. Moreover, independent studies in our laboratory have revealed additional MA mutants that are noninfectious even though they produce wild-type levels of particles (27). Hence, these studies provide evidence for an additional function for the MA protein of RSV.…”

Section: Discussionmentioning

confidence: 66%

“…Functional equivalents of these assembly domains have been found in the Gag proteins of unrelated retroviruses, including those of human im-munodeficiency virus (HIV) and murine leukemia virus. Moreover, these heterologous sequences can fully replace the RSV assembly functions in spite of their lack of sequence similarity (2,21,26,27).…”

mentioning

confidence: 99%

“…The former reside within a pair of amphipathic ␤ sheets on the surface of the protein and are thought to promote membrane binding through electrostatic interactions with negatively charged phospholipids on the cytoplasmic face of the plasma membrane (23,24,58). This membrane-binding domain can direct heterologous proteins (58), including RSV Gag (27), to the plasma membrane and thus can function independently of the rest of Gag.…”

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confidence: 99%

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A large region within the Rous sarcoma virus matrix protein is dispensable for budding and infectivity

Nelle

Wills

1996

J Virol

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All retroviruses have a layer of matrix protein (MA) situated directly beneath the lipid of their envelope. This protein is initially expressed as the amino-terminal sequence of the Gag polyprotein, where it plays an important role in binding Gag to the plasma membrane during the early steps of the budding process. Others have suggested that MA may provide additional functions during virion assembly, including the selective incorporation of viral glycoproteins and the RNA genome into the emerging virion. To further study the role of the Rous sarcoma virus MA sequence in the viral replication cycle, we have pursued an extensive deletion analysis. Surprisingly, the entire second half of MA (residues 87 to 155) and part of the neighboring p2 sequence were found to be dispensable not only for budding but also for infectivity in avian cells. Thus, all of the functions associated with the Rous sarcoma virus MA sequence must be contained within its first half.

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Section: Discussionmentioning

confidence: 66%

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confidence: 99%

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confidence: 99%

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A large region within the Rous sarcoma virus matrix protein is dispensable for budding and infectivity

Nelle

Wills

1996

J Virol

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“…One previous study showed that the second half of the MA protein of the oncoretrovirus RSV is dispensable for viral infectivity (Nelle and Wills, 1996). However, even small alterations in the N-terminal half of RSV MA completely abolished virus budding or infectivity (Nelle and Wills, 1996;Parent et al, 1996). In the case of HIV-1, relatively subtle alterations in MA often had drastic effects on HIV-1 morphogenesis and infectivity.…”

Section: Discussionmentioning

confidence: 99%

Efficient HIV-1 replication can occur in the absence of the viral matrix protein

et al. 1998

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Matrix (MA), a major structural protein of retroviruses, is thought to play a critical role in several steps of the HIV-1 replication cycle, including the plasma membrane targeting of Gag, the incorporation of envelope (Env) glycoproteins into nascent particles, and the nuclear import of the viral genome in nondividing cells. We now show that the entire MA protein is dispensable for the incorporation of HIV-1 Env glycoproteins with a shortened cytoplasmic domain. Furthermore, efficient HIV-1 replication in the absence of up to 90% of MA was observed in a cell line in which the cytoplasmic domain of Env is not required. Additional compensatory changes in Gag permitted efficient virus replication even if all of MA was replaced by a heterologous membrane targeting signal. Viruses which lacked the globular domain of MA but retained its N-terminal myristyl anchor exhibited an increased ability to form both extracellular and intracellular virus particles, consistent with a myristyl switch model of Gag membrane targeting. Pseudotyped HIV-1 particles that lacked the structurally conserved globular head of MA efficiently infected macrophages, indicating that MA is dispensable for nuclear import in terminally differentiated cells.

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“…for the N-terminal 100 residues of ASV Gag for budding of VLPs and weakly substitute for the N-terminal 10 residues (40). The N-terminal 32 residues of HIV-1 Gag contain three membrane-binding signals: the myr group, the conserved basic region, and a PI(4,5)P 2 -binding pocket (41,42).…”

Section: Determinants Of Asv Gag Plasma Membrane Targetingmentioning

confidence: 99%

The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery

Watanabe

Medina

Eastep

et al. 2018

Journal of Biological Chemistry

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Edited by Charles E. Samuel The Gag protein of avian sarcoma virus (ASV) lacks an N-myristoyl (myr) group, but contains structural domains similar to those of HIV-1 Gag. Similarly to HIV-1, ASV Gag accumulates on the plasma membrane (PM) before egress; however, it is unclear whether the phospholipid PI(4,5)P 2 binds directly to the matrix (MA) domain of ASV Gag, as is the case for HIV-1 Gag. Moreover, the role of PI(4,5)P 2 in ASV Gag localization and budding has been controversial. Here, we report that substitution of residues that define the PI(4,5)P 2-binding site in the ASV MA domain (reported in an accompanying paper) interfere with Gag localization to the cell periphery and inhibit the production of virus-like particles (VLPs). We show that co-expression of Sprouty2 (Spry2) or the pleckstrin homology domain of phospholipase C␦ (PH-PLC), two proteins that bind PI(4,5)P 2 , affects ASV Gag trafficking to the PM and budding. Replacement of the N-terminal 32 residues of HIV-1 MA, which encode its N-terminal myr signal and its PI(4,5)P 2-binding site, with the structurally equivalent N-terminal 24 residues of ASV MA created a chimera that localized at the PM and produced VLPs. In contrast, the homologous PI(4,5)P 2-binding signal in ASV MA could target HIV-1 Gag to the PM when substituted, but did not support budding. Collectively, these findings reveal a basic patch in both ASV and HIV-1 Gag capable of mediating PM binding and budding for ASV but not for HIV-1 Gag. We conclude that PI(4,5)P 2 is a strong determinant of ASV Gag targeting to the PM and budding. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2) 2 is an essential lipid in eukaryotic cells that functions in many differ

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Evidence for a second function of the MA sequence in the Rous sarcoma virus Gag protein

Cited by 52 publications

References 55 publications

A large region within the Rous sarcoma virus matrix protein is dispensable for budding and infectivity

A large region within the Rous sarcoma virus matrix protein is dispensable for budding and infectivity

Efficient HIV-1 replication can occur in the absence of the viral matrix protein

The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery

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