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PMID: 1404605 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation.

Journal of virology ·Vol. 66 ·No. 11 ·1992-11-00 ·Pages 6587-600

Li Y, Hui H, Burgess CJ, Price RW, Sharp PM, Hahn BH, Shaw GM

Abstract

Previous studies of the genetic and biologic characteristics of human immunodeficiency virus type 1 (HIV-1) have by necessity used tissue culture-derived virus. We recently reported the molecular cloning of four full-length HIV-1 genomes directly from uncultured human brain tissue (Y. Li, J. C. Kappes, J. A. Conway, R. W. Price, G. M. Shaw, and B. H. Hahn, J. Virol. 65:3973-3985, 1991). In this report, we describe the biologic properties of these four clones and the complete nucleotide sequences and genome organization of two of them. Clones HIV-1YU-2 and HIV-1YU-10 were 9,174 and 9,176 nucleotides in length, differed by 0.26% in nucleotide sequence, and except for a frameshift mutation in the pol gene in HIV-1YU-10, contained open reading frames corresponding to 5'-gag-pol-vif-vpr-tat-rev-vpu-env-nef-3' flanked by long terminal repeats. HIV-1YU-2 was fully replication competent, while HIV-1YU-10 and two other clones, HIV-1YU-21 and HIV-1YU-32, were defective. All three defective clones, however, when transfected into Cos-1 cells in any pairwise combination, yielded virions that were replication competent and transmissible by cell-free passage. The cellular host range of HIV-1YU-2 was strictly limited to primary T lymphocytes and monocyte-macrophages, a property conferred by its external envelope glycoprotein. Phylogenetic analyses of HIV-1YU-2 gene sequences revealed this virus to be a member of the North American/European HIV-1 subgroup, with specific similarity to other monocyte-tropic viruses in its V3 envelope amino acid sequence. These results indicate that HIV-1 infection of brain is characterized by the persistence of mixtures of fully competent, minimally defective, and more substantially altered viral forms and that complementation among them is readily attainable. In addition, the limited degree of genotypic heterogeneity observed among HIV-1YU and other brain-derived viruses and their preferential tropism for monocyte-macrophages suggest that viral replication within the central nervous system may differ from that within the peripheral lymphoid compartment in significant and clinically important ways. The availability of genetically and biologically well characterized HIV-1 clones from uncultured human tissue should facilitate future studies of virus-cell interactions relevant to viral pathogenesis and drug and vaccine development.

MeSH Terms
AIDS Dementia Complex/microbiology Adult Amino Acid Sequence Base Sequence Brain/microbiology Cells, Cultured Cloning, Molecular Defective Viruses/genetics Frameshift Mutation Genes, Viral/genetics Genetic Complementation Test Genetic Variation Genome, Viral Genotype HIV-1/genetics Humans Leukocytes/microbiology Macrophages/microbiology Male Molecular Sequence Data Open Reading Frames/genetics Organ Specificity Phylogeny Sequence Homology, Nucleic Acid Virus Replication/genetics
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Li Y
Department of Medicine, University of Alabama, Birmingham 35294-0007.
Hui H
Burgess C J
Price R W
Sharp P M
Hahn B H
Shaw G M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.11.6587-6600.1992
Published
1992-11-00
Pages
6587-600
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240154
Subset
IM
Grants
NIAID NIH HHS · AI27290 · United States
NIAID NIH HHS · AI27767 · United States
NINDS NIH HHS · NS25701 · United States
Databases
GENBANK
M93258, M93259
External Links
PubMed source DOI: 10.1128/JVI.66.11.6587-6600.1992 PMC Full Text View journal details
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