An essential role for the His-8 residue of the SDF-1α–chimeric, tropism-redirected Env protein of the Moloney murine leukemia virus in regulating postbinding fusion events

ABSTRACT Fusion of the membrane of the Moloney murine leukemia virus (Mo-MLV) Env protein is facilitated by cleavage of the R peptide from the cytoplasmic tail of its TM subunit, but the mechanism for this effect has remained obscure. The fusion is also controlled by the isomerization of the intersubunit disulfide of the Env SU-TM complex. In the present study, we used several R-peptide-cleavage-inhibited virus mutants to show that the R peptide suppresses the isomerization reaction in both in vitro and in vivo assays. Thus, the R peptide affects early steps in the activation pathway of murine leukemia virus Env.

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Threshold Number of Provirus Copies Required per Cell for Efficient Virus Production and Interference in Moloney Murine Leukemia Virus-Infected NIH 3T3 Cells

Journal of Virology ◽

10.1128/jvi.72.7.5414-5424.1998 ◽

1998 ◽

Vol 72 (7) ◽

pp. 5414-5424 ◽

Cited By ~ 5

Author(s):

Takashi Odawara ◽

Masamichi Oshima ◽

Kent Doi ◽

Aikichi Iwamoto ◽

Hiroshi Yoshikura

Keyword(s):

Murine Leukemia Virus ◽

Leukemia Virus ◽

Natural Infection ◽

Mrna Level ◽

Virus Production ◽

Threshold Level ◽

Moloney Murine Leukemia Virus ◽

Sigmoid Curve ◽

Env Protein ◽

Murine Leukemia

ABSTRACT The gag-pol readthrough mutant of Moloney murine leukemia virus, MLV-B(CAG) (T. Odawara, H. Yoshikura, M. Oshima, T. Tanaka, D. S. Jones, F. Nemoto, Y. Kuchino, and A. Iwamoto, J. Virol. 65:6376–6379, 1991), was poorly complemented by a mutant encoding only Gag. This is because with all the genetic elements necessary for env expression present in MLV-B(CAG), insufficient Env protein was produced by the cells expressing MLV-B(CAG) for efficient virus production. Since the envmRNA expression per provirus in the MLV-B(CAG)- and wild-type-MLV-producing cells were the same and since the cells expressing the former contained eightfold fewer proviral copies, the insufficient Env expression by the former was found to be due to insufficient proviral copies in the cells. Examination of the cell clones having various proviral copies of Δwt MLV (M. Oshima, T. Odawara, T. Matano, H. Sakahira, Y. Kuchino, A. Iwamoto, and H. Yoshikura, J. Virol. 70:2286–2295, 1996) showed that mRNA level was proportional to the number of proviral copies while interference and virus production followed a sigmoid curve with a sharp rise at the threshold number of proviral copies of around four per cell. Multicycle infection probably continues until the threshold level of proviral copies is attained in natural infection too.

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Cytoplasmic Tail of Moloney Murine Leukemia Virus Envelope Protein Influences the Conformation of the Extracellular Domain: Implications for Mechanism of Action of the R Peptide

Journal of Virology ◽

10.1128/jvi.77.2.1281-1291.2003 ◽

2003 ◽

Vol 77 (2) ◽

pp. 1281-1291 ◽

Cited By ~ 60

Author(s):

Hector C. Aguilar ◽

W. French Anderson ◽

Paula M. Cannon

Keyword(s):

Murine Leukemia Virus ◽

Leukemia Virus ◽

Cytoplasmic Tail ◽

Moloney Murine Leukemia Virus ◽

Virus Envelope ◽

Peptide Cleavage ◽

Virus Envelope Protein ◽

Env Protein ◽

Membrane Spanning ◽

Murine Leukemia

ABSTRACT The envelope (Env) protein of Moloney murine leukemia virus (MoMuLV) is a homotrimeric complex whose monomers consist of linked surface (SU) and transmembrane (TM) proteins cleaved from a precursor protein by a cellular protease. In addition, a significant fraction of virion-associated TM is further processed by the viral protease to remove the C-terminal 16 amino acids of the cytoplasmic domain, the R peptide. This cleavage greatly enhances the fusogenicity of the protein and is necessary for the formation of a fully functional Env protein complex. We have previously proposed that R peptide cleavage enhances fusogenicity by altering the conformation of the ectodomain of the protein (Y. Zhao et al., J. Virol. 72:5392-5398, 1998). Using a series of truncation and point mutants of MoMuLV Env, we now provide direct biochemical and immunological evidence that the cytoplasmic tail and the membrane-spanning region of Env can influence the overall structure of the ectodomain of the protein and alter the strength of the SU-TM interaction. The R-peptide-truncated form of the protein, in particular, exhibits a markedly different conformation than the full-length protein.

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