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

Nelle, Timothy D.; Wills, John W.

doi:10.1128/jvi.70.4.2269-2276.1996

Cited by 44 publications

(36 citation statements)

References 55 publications

(96 reference statements)

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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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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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“…4A). The remainder of MA, however, is dispensable for budding and infectivity (40,59,63). Comparison of the predicted sequence of the first 86 amino acids of the ev/J MA-coding region with that of RSV shows a 58% level of identity and 72% level of similarity, while the remaining portion of MA shows only 24 and 34% levels of identity and similarity, respectively, between these proteins.…”

Section: Structure Of Ev/j Proviruses In Phage Genomic Clonesmentioning

confidence: 99%

“…MA. Studies with the RSV Gag protein have demonstrated that the first 86 amino acids of MA are required for efficient particle formation and for association of the Gag polyprotein with the plasma membrane (40,59); this region is therefore referred to as the M region (Fig. 4A).…”

Section: Structure Of Ev/j Proviruses In Phage Genomic Clonesmentioning

confidence: 99%

Genome Structure and Expression of the ev/J Family of Avian Endogenous Viruses

Ruis

Benson

Conklin

1999

J Virol

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We recently reported the identification of sequences in the chicken genome that show over 95% identity to the novel envelope gene of the subgroup J avian leukosis virus (S. J. Benson, B. L. Ruis, A. M. Fadly, and K. F. Conklin, J. Virol. 72:10157-10164, 1998). Based on the fact that the endogenous subgroup J-related env genes were associated with long terminal repeats (LTRs), we concluded that these LTR-env sequences defined a new family of avian endogenous viruses that we designated the ev/J family. In this report, we have further characterized the content and expression of the ev/J proviruses. The data obtained indicate that there are between 6 and 11 copies of ev/J proviruses in all chicken cells examined and that these proviruses fall into six classes. Of the 18 proviruses examined, all share a high degree of sequence identity and all contain an internal deletion that removes all of the pol gene and various amounts of gag and env gene sequences. Sequencing of the gag genes, LTRs, and untranslated regions of several ev/J proviruses revealed a high level of identity between isolates, indicating that they have not undergone significant sequence variation since their introduction into the avian germ line. Although the ev/J gag gene showed a relatively weak relationship (46% identity and 61% similarity at the amino acid level) to that of the avian leukosis-sarcoma virus family, it retains several sequences of demonstrated importance for virus assembly, budding, and/or infectivity. Finally, evidence was obtained that at least some members of the ev/J family are expressed and, if translated, could encode Gag-and Env-related polypeptides.

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“…The M domain takes the Gag protein to the cytoplasmic face of the plasma membrane and is the focus of the present report. It is located at the N terminus of Gag, and its sequence is a subset of the MA sequence (24). All mutants that are defective in the M domain can be rescued by complementation with budding-competent Gag molecules, indicating that downstream assembly functions are not disrupted (51).…”

mentioning

confidence: 99%

“…To test this hypothesis, we examined the M domain of the RSV Gag protein, which appears to be very different from the HIV-1 M domain in that it is large (86 residues [24]) and not myristylated. Although the RSV M domain contains 11 basic residues, they are scattered throughout the sequence without any obvious clusters.…”

mentioning

confidence: 99%

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

Parent

Wilson

Resh

et al. 1996

J Virol

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During retrovirus assembly, Gag proteins bind to the inner leaflet of the plasma membrane to initiate the budding process. The molecular basis of this protein-lipid interaction is poorly understood. For the human immunodeficiency virus type 1 Gag protein, we recently reported that the membrane-binding domain resides within the N-terminal 31 amino acids and consists of two components: myristate and a cluster of basic residues, which together promote membrane binding in vitro and budding in vivo (W. Zhou, L. J. Parent, J. W. Wills, and M. D. Resh, J. Virol. 68:2556-2569, 1994). The positively charged residues associate electrostatically with acidic phospholipids to stabilize membrane binding, while myristate provides membrane-binding energy via hydrophobic interactions. Here we demonstrate that the human immunodeficiency virus type 1 Gag membranebinding domain can fully replace the membrane-targeting function of the N-terminal 100 residues of the nonmyristylated Rous sarcoma virus (RSV) Gag protein. To further explore the importance of myristate and basic residues in membrane binding, we developed a gain-of-function assay whereby budding was restored to defective mutants of RSV Gag. Detailed mutational analysis revealed that the position, number, and context of charged residues are crucial to budding. Myristate provides additional membrane-binding energy, which is critical when a Gag protein is near the threshold of stable membrane association. Finally, viruses with altered matrix (MA) proteins that are noninfectious, even though they produce particles with high efficiency, were identified. Thus, we present the first evidence that the RSV MA sequence plays two distinct roles, membrane binding during particle assembly and a second, as yet undefined function required for viral infectivity.

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

Cited by 44 publications

References 55 publications

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

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

Genome Structure and Expression of the ev/J Family of Avian Endogenous Viruses

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

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