Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
Identification of individual amino acids within the V3 region determining syncytium formation and replication rate of viruses chimeric for V3.
Int Conf AIDS. 1992 Jul 19-24;8(1):Mo20 (abstract no. MoA 0073). Unique Identifier : AIDSLINE ICA8/92400029 De Jong J; De Ronde A; Keulen W; Tersmette M; Goudsmit J; HRL, UvA, Amsterdam, The Netherlands.
Abstract:
OBJECTIVES: Determination of position and kind of amino acids within the V3 region associated with the syncytium forming capacity and replication rate of V3-chimeric viruses. METHODS: V3 regions differing in four amino acids derived from a non-syncytium inducing (168.1/NSI) and a syncytium inducing isolate (168.10/SI) of one individual, were cloned into a full-length HXB-2 molecular clone. Transfection in SupT1-cells generated HXB-2 viruses, only differing in the V3 region. The phenotype of each chimeric virus corresponded with the phenotype of the virus from which its V3 region was derived. TABULAR DATA, SEE ABSTRACT VOLUME. To determine the minimal amino acid changes responsible for the observed phenotype change, a set of chimeric viruses (2(4)) covering all possible combinations of the four amino acid changes was constructed by PCR. The complete set of molecular clones was transfected by electroporation in SupT1-cells; syncytia formation as well as p24 core antigen production were monitored for 14 days after transfection. RESULTS: Of the molecular clones containing single amino acid changes only the R (168.1/R) at position 11 was able to confer the syncytium inducing/fast replicating phenotype to 168.1. Transfection of the 168.10 molecular clone resulted in the killing of all SupT1-cells by massive syncytia formation. Transfection of the 168.1/R molecular clone did not cause the killing of all the transfected cells, because the initially formed syncytia disappeared after 12 days of cultivation. The complete 168.10 phenotype was obtained when, in addition to the R mutation, one extra mutation, with the exception of the T at position 22, was generated. CONCLUSIONS: The R amino acid at position 11 is the most important contributor to the switch from the 168.1/NSI to the 168.10/SI phenotype. However, to obtain the complete 168.10/SI phenotype one additional mutation, at position 25 or at the not previously described position 29, is necessary.
Keywords: Amino Acid Sequence Cell Fusion/*GENETICS Cells, Cultured Comparative Study Cytopathogenic Effect, Viral/*GENETICS Human HIV Envelope Protein gp120/*GENETICS/PHYSIOLOGY HIV-1/GENETICS/*PHYSIOLOGY Molecular Sequence Data Peptide Fragments/*GENETICS/PHYSIOLOGY Phenotype Recombinant Fusion Proteins/GENETICS Transfection Virus Replication/*GENETICS ABSTRACT 921230
M92C5318
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
