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Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.

Publication ,  Journal Article
Gao, F; Morrison, SG; Robertson, DL; Thornton, CL; Craig, S; Karlsson, G; Sodroski, J; Morgado, M; Galvao-Castro, B; von Briesen, H; Beddows, S ...
Published in: J Virol
March 1996

Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HIV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HIV-1 group M (clades A to G), as well as an intersubtype recombinant (F/B) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay. This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env genes of primary HIV-1 isolates collected worldwide can vary considerably in their genetic, phylogenetic, and biological properties. The panel of env constructs described here should prove valuable for future structure-function studies of naturally occurring envelope glycoproteins as well as AIDS vaccine development efforts targeted against a broader spectrum of viruses.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

March 1996

Volume

70

Issue

3

Start / End Page

1651 / 1667

Location

United States

Related Subject Headings

  • Virology
  • Tunicamycin
  • Sequence Homology, Nucleic Acid
  • Sequence Homology, Amino Acid
  • Recombination, Genetic
  • Protein Precursors
  • Polymerase Chain Reaction
  • Phylogeny
  • Molecular Sequence Data
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Gao, F., Morrison, S. G., Robertson, D. L., Thornton, C. L., Craig, S., Karlsson, G., … Hahn, B. H. (1996). Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization. J Virol, 70(3), 1651–1667. https://doi.org/10.1128/JVI.70.3.1651-1667.1996
Gao, F., S. G. Morrison, D. L. Robertson, C. L. Thornton, S. Craig, G. Karlsson, J. Sodroski, et al. “Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.J Virol 70, no. 3 (March 1996): 1651–67. https://doi.org/10.1128/JVI.70.3.1651-1667.1996.
Gao F, Morrison SG, Robertson DL, Thornton CL, Craig S, Karlsson G, Sodroski J, Morgado M, Galvao-Castro B, von Briesen H, Beddows S, Weber J, Sharp PM, Shaw GM, Hahn BH. Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization. J Virol. 1996 Mar;70(3):1651–1667.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

March 1996

Volume

70

Issue

3

Start / End Page

1651 / 1667

Location

United States

Related Subject Headings

  • Virology
  • Tunicamycin
  • Sequence Homology, Nucleic Acid
  • Sequence Homology, Amino Acid
  • Recombination, Genetic
  • Protein Precursors
  • Polymerase Chain Reaction
  • Phylogeny
  • Molecular Sequence Data
  • Humans