Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac

Babak Banapour, Marta Marthas, Ross A. Ramos, Barbara L. Lohman, Ronald E. Unger, Murray B. Gardner, Niels C Pedersen, Paul A Luciw

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Abstract

Simian immunodeficiency virus (SIV), a lytnphocytopathic lentivirus, induces an AIDS-like disease in rhesus macaques (Macaco mulatto). A pathogenic molecular clone of rhesus macaque SIV (SIVmac), SIVmac-239, replicates and induces cytopathology in T lymphocytes but is restricted for replication in macrophages. In contrast, a nonpathogenic molecular clone of SIVmac, SIVmac-1A11, replicates and induces syncytia (multinucleated giant cells) in cultures of both T lymphocytes and macrophages. SIVmac-1A11 does not cause disease in macaques. To map the viral determinants of macrophage tropism, reciprocal recombinant genomes were constructed between molecular clones of SIVmac-239 and SIVmac-1A11. Infectious recombinant viruses were rescued by transfection of cloned viral genomes into permissive lymphoid cells. Analysis of one pair of reciprocal recombinants revealed that an internal 6.2-kb DNA fragment of SIVmac-1A11 was necessary and sufficient for both syncytium formation and efficient replication in macrophages. This region includes the coding sequences for a portion of the gag gene, all of the pol, vif, vpr, and vpx genes, the first coding exons of tat and rev, and the external env glycoprotein gp130. Thus, the transmembrane glycoprotein of env, the nef gene, the second coding exons of tat and rev, and the long terminal repeats are not essential for in vitro macrophage tropism. Analysis of additional recombinants revealed that syncytium formation, but not virus production, was controlled by a 1.4-kb viral DNA fragment in SIVmac-1A11 encoding only the external env glycoprotein gp130. Thus, gp130 env of SIVmac-1A11 is necessary for entry of virus into macrophages but is not sufficient for a complete viral replication cycle in this cell type. We therefore conclude that gp130 env and one or more genetic elements (exclusive of the long terminal repeats, transmembrane glycoprotein of env, and second coding exons of tat and rev, and nef) are essential for a complete replication cycle of SIVmac in rhesus macaque macrophages.

Original languageEnglish (US)
Pages (from-to)5798-5805
Number of pages8
JournalJournal of Virology
Volume65
Issue number11
StatePublished - Nov 1991

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
tropisms
Tropism
macrophages
Macrophages
giant cells
Giant Cells
env Gene Products
glycoproteins
Macaca mulatta
exons
Exons
terminal repeat sequences
Terminal Repeat Sequences
Clone Cells
clones
viruses
nef Genes
T-lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Banapour, B., Marthas, M., Ramos, R. A., Lohman, B. L., Unger, R. E., Gardner, M. B., ... Luciw, P. A. (1991). Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. Journal of Virology, 65(11), 5798-5805.

Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. / Banapour, Babak; Marthas, Marta; Ramos, Ross A.; Lohman, Barbara L.; Unger, Ronald E.; Gardner, Murray B.; Pedersen, Niels C; Luciw, Paul A.

In: Journal of Virology, Vol. 65, No. 11, 11.1991, p. 5798-5805.

Research output: Contribution to journalArticle

Banapour B, Marthas M, Ramos RA, Lohman BL, Unger RE, Gardner MB et al. Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. Journal of Virology. 1991 Nov;65(11):5798-5805.
Banapour, Babak ; Marthas, Marta ; Ramos, Ross A. ; Lohman, Barbara L. ; Unger, Ronald E. ; Gardner, Murray B. ; Pedersen, Niels C ; Luciw, Paul A. / Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. In: Journal of Virology. 1991 ; Vol. 65, No. 11. pp. 5798-5805.
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abstract = "Simian immunodeficiency virus (SIV), a lytnphocytopathic lentivirus, induces an AIDS-like disease in rhesus macaques (Macaco mulatto). A pathogenic molecular clone of rhesus macaque SIV (SIVmac), SIVmac-239, replicates and induces cytopathology in T lymphocytes but is restricted for replication in macrophages. In contrast, a nonpathogenic molecular clone of SIVmac, SIVmac-1A11, replicates and induces syncytia (multinucleated giant cells) in cultures of both T lymphocytes and macrophages. SIVmac-1A11 does not cause disease in macaques. To map the viral determinants of macrophage tropism, reciprocal recombinant genomes were constructed between molecular clones of SIVmac-239 and SIVmac-1A11. Infectious recombinant viruses were rescued by transfection of cloned viral genomes into permissive lymphoid cells. Analysis of one pair of reciprocal recombinants revealed that an internal 6.2-kb DNA fragment of SIVmac-1A11 was necessary and sufficient for both syncytium formation and efficient replication in macrophages. This region includes the coding sequences for a portion of the gag gene, all of the pol, vif, vpr, and vpx genes, the first coding exons of tat and rev, and the external env glycoprotein gp130. Thus, the transmembrane glycoprotein of env, the nef gene, the second coding exons of tat and rev, and the long terminal repeats are not essential for in vitro macrophage tropism. Analysis of additional recombinants revealed that syncytium formation, but not virus production, was controlled by a 1.4-kb viral DNA fragment in SIVmac-1A11 encoding only the external env glycoprotein gp130. Thus, gp130 env of SIVmac-1A11 is necessary for entry of virus into macrophages but is not sufficient for a complete viral replication cycle in this cell type. We therefore conclude that gp130 env and one or more genetic elements (exclusive of the long terminal repeats, transmembrane glycoprotein of env, and second coding exons of tat and rev, and nef) are essential for a complete replication cycle of SIVmac in rhesus macaque macrophages.",
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