Mutations in the cytoplasmic tail of influenza A virus neuraminidase affect incorporation into virions

Bilsel, Pamuk; Castrucci, Maria Rita; Kawaoka, Yoshihiro

doi:10.1128/jvi.67.11.6762-6767.1993

Cited by 37 publications

(24 citation statements)

References 44 publications

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“…Despite the possibility that HA-spikeless A/WSN/33 ts6 Is virions released from cells at the non-permissive temperature may contain an HA transmembrane domain and cytoplasmic tail fragment, the particles contained twice the normal amount of NA (Pattnaik et al, 1986). Other intriguing observations that may relate to a functional role of the NA cytoplasmic tail in virus budding are: (i) the NAinfluenza virus produced by Liu and Air (1993) retained an RNA fragment which has the potential to encode the cytoplasmic tail of NA and (ii) the report of negative data that it was not possible to obtain a tail-NA transfectant virus (Bilsel et al, 1993). The influenza virus M, protein is a minor component of the viral envelope (Zebedee and Lamb, 1988) and its cytoplasmic tail is relatively long, containing 54 residues .…”

Section: Discussionmentioning

confidence: 99%

The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity.

1994

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The influenza A virus hemagglutinin (HA) glycoprotein contains a cytoplasmic tail which consists of 10‐11 amino acids, of which five residues re conserved in all subtypes of influenza A virus. As the cytoplasmic tail is not needed for intracellular transport to the plasma membrane, it has become virtually dogma that the role of the cytoplasmic tail is in forming protein‐protein interactions necessary for creating an infectious budding virus. To investigate the role of the HA cytoplasmic tail in virus replication, reverse genetics was used to obtain an influenza virus that lacked an HA cytoplasmic tail. The rescued virus contained the HA of subtype A/Udorn/72 in a helper virus (subtype A/WSN/33) background. Biochemical analysis indicated that only the introduced tail‐ HA was incorporated into virions and these particles lacked a detectable fragment of the helper virus HA. The tail‐ HA rescued virus assembled and replicated almost as efficiently as virions containing wild‐type HA, suggesting that the cytoplasmic tail is not essential for the virus assembly process. Nonetheless, a revertant virus was isolated, suggesting that possession of a cytoplasmic tail does confer an advantage.

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Section: Discussionmentioning

confidence: 99%

The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity.

1994

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“…the cytoplasmic domain led to reduced incorporation of NA into the viral envelope, the release of particles that had an aberrant pleomorphic instead of wild-type spherical morphology, and a diminished particle infectivity (8,28,39). The observed phenotypes were attributed to an impaired interaction of NA and the matrix protein M1 resulting in aberrant particle assembly.…”

mentioning

confidence: 99%

The Cytoplasmic Domain of Marburg Virus GP Modulates Early Steps of Viral Infection

Mittler

Kolesnikova

Hartlieb

et al. 2011

J Virol

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Marburg virus infection is mediated by the only viral surface protein, GP, a trimeric type I transmembrane protein. While its ectodomain mediates receptor binding and fusion of viral and cellular membranes and its transmembrane domain is essential for the recruitment of GP into budding particles by the matrix protein VP40, the role of the short cytoplasmic domain has remained enigmatic. Here we show that a missing cytoplasmic domain did not impair trimerization, intracellular transport, or incorporation of GP into infectious Marburg virus-like particles (iVLPs) but altered the glycosylation pattern as well as the recognition of GP by neutralizing antibodies. These results suggest that subtle conformational changes took place in the ectodomain. To investigate the function of the cytoplasmic domain during viral entry, a novel entry assay was established to monitor the uptake of filamentous VLPs by measuring the occurrence of luciferase-labeled viral nucleocapsids in the cytosol of target cells. This quantitative assay showed that the entry process of VLPs incorporating GP missing its cytoplasmic domain (GP⌬CD) was impaired. Supporting these results, iVLPs incorporating a mutant GP missing its cytoplasmic domain were significantly less infectious than iVLPs containing wild-type GP. Taken together, the data indicate that the absence of the short cytoplasmic domain of Marburg virus GP may induce conformational changes in the ectodomain which impact the filoviral entry process.

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“…These proteins are synthesized in the rough endoplasmic reticulum of the infected cell, processed during trafficking along the exocytic pathway, and selectively incorporated into budding virions. During viral assembly, interactions between the cytoplasmic domains of these envelope glycoproteins and internal proteins of the virion likely influence the site of viral budding (Rhee and Hunter, 1990;Owens et al, 1991;Lodge et al, 1994), the incorporation of envelope proteins into virions (Whitt et al, 1989;Gaedigk-Nitschko and Schlesinger, 1991;Lyles et al, 1992;Bilsel et al, 1993;Gray and Roth, 1993;Naim and Roth, 1993;Zhao et al, 1994), and the infectivity of the viral particle (Granowitz et al, 1991;Dubay et al, 1992;Johnston et al, 1993;Yu et al, 1992Yu et al, , 1993Owens and Rose, 1993;Brody et al, 1994;Zhao et al, 1994). There is also increasing evidence that envelope glycoproteins interact with cellular proteins that affect their transport to, mobility and expression on the cell surface (Doyle et al, 1985;Lazarovits et al, 1990;Lydy and Compans, 1993).…”

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confidence: 99%

An internalization signal in the simian immunodeficiency virus transmembrane protein cytoplasmic domain modulates expression of envelope glycoproteins on the cell surface.

Sauter

Pelchen–Matthews

Bron

et al. 1996

The Journal of Cell Biology

139

183

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Abstract. A Tyr to Cys mutation at amino acid position 723 in the cytoplasmic domain of the simian immunodeficiency virus (sir) transmembrane (TM) molecule has been shown to increase expression of envelope glycoproteins on the surface of infected cells. Here we show that Tyr-723 contributes to a sorting signal that directs the rapid endocytosis of viral glycoproteins from the plasma membrane via coated pits. On ceils infected by SIVs with a Tyr at position 723, envelope glycoproteins were transiently expressed on the cell surface and then rapidly endocytosed. Similar findings were noted for envelope molecules expressed in the absence of other viral proteins. Immunoelectron microscopy demonstrated that these molecules were localized in patches on the cell surface and were frequently associated with coated pits. In contrast, envelope glycoproteins containing a Y723C mutation were diffusely distributed over the entire plasma membrane. To determine if an internalization signal was present in the SIV TM, chimeric molecules were constructed that contained the CD4 external and membrane spanning domains and a SIV TM cytoplasmic tail with a Tyr or other amino acids at SIV position 723. In Hela cells stably expressing these molecules, chimeras with a Tyr-723 were rapidly endocytosed, while chimeras containing other amino acids at position 723, including a Phe, were internalized at rates only slightly faster than a CD4 molecule that lacked a cytoplasmic domain. In addition, the biological effects of the internalization signal were evaluated on infectious viruses. A mutation that disrupted the signal and as a result, increased the level of viral envelope glycoprotein on infected cells, was associated with accelerated infection kinetics and increased cell fusion during viral replication. These resuits demonstrate that a Tyr-dependent motif in the SIV TM cytoplasmic domain can function as an internalization signal that can modulate expression of the viral envelope molecules on the cell surface and affect the biological properties of infectious viruses. The conservation of an analogous Tyr in all human and simian immunodeficiency viruses suggests that this signal may be present in other primate lentiviruses and could be important in the pathogenesis of these viruses in vivo.

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Mutations in the cytoplasmic tail of influenza A virus neuraminidase affect incorporation into virions

Abstract: The significance of the conserved cytoplasmic tail sequence of influenza A virus neuraminidase (NA) was analyzed by the recently developed reverse genetics technique (W.

Cited by 37 publications

References 44 publications

The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity.

The influenza virus hemagglutinin cytoplasmic tail is not essential for virus assembly or infectivity.

The Cytoplasmic Domain of Marburg Virus GP Modulates Early Steps of Viral Infection

An internalization signal in the simian immunodeficiency virus transmembrane protein cytoplasmic domain modulates expression of envelope glycoproteins on the cell surface.

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