Tanya Pfeiffer

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We have examined the role of the membrane-anchoring domain of the HIV-1 glycoproteins in viral glycoprotein function, glycoprotein incorporation, and viral infectivity. For this purpose, we initially exchanged the entire membrane-spanning region with that from a cellular glycoprotein (CD22). Subsequently, the strictly conserved arginine in the central(More)
HIV-derived vectors are of potential clinical relevance due to their ability to transduce nondividing cells in vitro and in vivo. However, the generation of cell lines stably and reproducibly expressing high amounts of defined subviral particles, capable of packaging and transducing HIV-derived vectors, has been hampered by the cytotoxicity of some of the(More)
Five in-frame stop mutations in the HIV-1 env gene, which lead to the production of env gene products truncated within the cytoplasmic C-terminal tail, have been generated and their effects on membrane fusion capacity, glycoprotein incorporation into virus particles, infectivity, and cytopathogenicity were analyzed. The resulting truncated glycoproteins(More)
The self-assembling protein nanoparticle (SAPN) is an antigen-presenting system that has been shown to be suitable for use as a vaccine platform. The SAPN scaffold is based on the principles of icosahedral symmetry, beginning from a monomeric chain that self-assembles into an ordered oligomeric state. The monomeric chain contains two covalently linked(More)
Our studies aim to elucidate the functions carried out by the very long, and in its length highly conserved, C-terminal cytoplasmic domain (Env-CT) of the HIV-1 glycoprotein. Mass spectrometric analysis of cellular proteins bound to a tagged version of the HIV Env-CT led to the identification of the prohibitin 1 and 2 proteins (Phb1 and Phb2). These(More)
Mutant HIV (HIV-Env-Tr712) lacking the cytoplasmic tail of the viral glycoprotein (Env-CT) exhibits a cell-type specific replication phenotype such that replicative spread occurs in some T-cell lines (referred to as permissive cells) but fails to do so in most T-cell lines or in PBMCs (referred to as non-permissive cells). We aim to gain insight on the(More)
In this study, specific signals known to mediate endoplasmic reticulum or Golgi localization of transmembrane proteins have been transferred to the human immunodeficiency virus type 1 (HIV-1) env gene product. The intracellularly retained recombinant glycoproteins were not proteolytically processed to gp120 and gp41, which is further evidence that this(More)
A long cytoplasmic C-terminus (Env-CT) on the human immunodeficiency virus type 1 (HIV-1) Env protein is a highly conserved feature in vivo. Mutant HIV lacking the Env-CT cannot replicate in PBMCs and in the majority of T cell lines (nonpermissive cells, e.g., H9 cells) in vitro. We report here that a single amino acid change (N750K) in the context of the(More)
In certain cell systems, exchange of the human immunodeficiency virus (HIV) Env signal peptide (SP) sequence with that of heterologous SPs has been shown to increase gp120 transport and secretion. Here we demonstrate that exchange of the HIV-Env-SP with those from erythropoietin or tissue plasminogen activator in the proviral context does not increase(More)
Immune responses to a pseudovirion-based HIV vaccine enriched in Env conformations, which have been induced to an authentic intermediate fusion stage by interaction with the cellular HIV receptor complex, have been analysed in human CD4/CCR5-transgenic rats. High titre Env-binding antibodies were elicited. However, these immune sera failed to neutralise(More)