Genetic determinants of SIVmac macrophage tropism map to env.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

Genetic determinants of SIVmac macrophage tropism map to env.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:20 (abstract no. 4). Unique Identifier : AIDSLINE PRIM8/900004
Mori K; Sehgal P; Ringler D; Desrosiers R; New England Regional Primate Research Center

Abstract: A molecular clone of SIVmac239 produces virus which causes AIDS in rhesus monkeys in a time frame suitable for laboratory investigation. This cloned virus replicates well in primary PBL cultures and in CD4+ lymphoid cell lines but it replicates poorly in cultured macrophages. We have used primary alveolar macrophages taken by lung lavage from healthy, uninfected rhesus monkeys for these studies. At the time of death of one rhesus monkey (#316) infected with cloned SIVmac239, numerous infected macrophages were noted in the lung and brain. Virus recovered from the lung of this animal (SIVmac316) replicates at least two orders of magnitude better in cultured macrophages than the parent cloned virus SIVmac239. SIVmac316 also replicates well in lymphocytes. LTR clones of SIVmac316 when exchanged into SIVmac239 did not confer ability to replicate in macrophages. Twelve env clones of SIVmac316 were exchanged into SIVmac239 but only two of these were replication competent. Exchange of these env sequences into SIVmac239 increased ability to replicate in macrophages by at least two orders of magnitude. Although sequences to the left of env in SIVmac316 can contribute to macrophage tropism, the major determinants in this system are located in the env gene. DNA sequencing revealed eight amino acid changes between SIVmac239 and 316 distributed over the full length of env. Construction of additional recombinants demonstrated that changes in both the SU (gp120) and TM (gp41) contributed to ability to replicate in macrophages. Continued study in this system will allow detailed understanding of the role of viral env proteins in lymphocyte vs macrophage infection. Furthermore, these closely-matched cloned reagents will allow investigation of the significance of macrophage tropism for pathogenic potential, persistence and disease manifestations.

Keywords: Animal Brain/MICROBIOLOGY Cloning, Molecular *DNA Replication DNA, Viral/BIOSYNTHESIS/CHEMISTRY *Genes, env Genetic Markers Lung/MICROBIOLOGY Macaca mulatta Macrophages/*MICROBIOLOGY Recombinant Proteins/BIOSYNTHESIS/GENETICS Repetitive Sequences, Nucleic Acid Simian Acquired Immunodeficiency Syndrome/GENETICS SIV/GROWTH & DEVELOPMENT/*GENETICS Tumor Cells, Cultured Virus Replication/*GENETICS ABSTRACT
910730
M9170990

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