Abstract
We have recently reported the isolation and molecular cloning of a human immunodeficiency virus type 1 isolate (HIV-1 DH125) that exhibits rapid replication kinetics and marked cytopathicity in both human and chimpanzee peripheral blood mononuclear cells (PBMC). To identify the viral determinants responsible for infectivity of chimpanzee PBMC, chimeric viruses containing the following components were constructed: (i) the entire envelope gene; (ii) gp120 sequences; (iii) gp41 sequences; and (iv) individual or various combinations of the gp120 variable regions of HIV-1 DH125 inserted into the backbone of another HIV-1 isolate (HIV-1 AD8), which is unable to infect chimpanzee PBMC. Analyses of virus replication kinetics in human and chimpanzee PBMC revealed that gp120 contains determinants which confer infectivity for chimpanzee PBMC and that the capacity to establish such an infection requires the cooperative interaction between multiple variable regions of the HIV-1 DH125 gp120.
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Selected References
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- Carrillo A., Ratner L. Cooperative effects of the human immunodeficiency virus type 1 envelope variable loops V1 and V3 in mediating infectivity for T cells. J Virol. 1996 Feb;70(2):1310–1316. doi: 10.1128/jvi.70.2.1310-1316.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carrillo A., Ratner L. Human immunodeficiency virus type 1 tropism for T-lymphoid cell lines: role of the V3 loop and C4 envelope determinants. J Virol. 1996 Feb;70(2):1301–1309. doi: 10.1128/jvi.70.2.1301-1309.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freed E. O., Martin M. A. Evidence for a functional interaction between the V1/V2 and C4 domains of human immunodeficiency virus type 1 envelope glycoprotein gp120. J Virol. 1994 Apr;68(4):2503–2512. doi: 10.1128/jvi.68.4.2503-2512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fultz P. N. Nonhuman primate models for AIDS. Clin Infect Dis. 1993 Aug;17 (Suppl 1):S230–S235. doi: 10.1093/clinids/17.supplement_1.s230. [DOI] [PubMed] [Google Scholar]
- Ghosh S. K., Fultz P. N., Keddie E., Saag M. S., Sharp P. M., Hahn B. H., Shaw G. M. A molecular clone of HIV-1 tropic and cytopathic for human and chimpanzee lymphocytes. Virology. 1993 Jun;194(2):858–864. doi: 10.1006/viro.1993.1331. [DOI] [PubMed] [Google Scholar]
- Koito A., Harrowe G., Levy J. A., Cheng-Mayer C. Functional role of the V1/V2 region of human immunodeficiency virus type 1 envelope glycoprotein gp120 in infection of primary macrophages and soluble CD4 neutralization. J Virol. 1994 Apr;68(4):2253–2259. doi: 10.1128/jvi.68.4.2253-2259.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. doi: 10.1128/jvi.61.2.570-578.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schuitemaker H., Meyaard L., Kootstra N. A., Dubbes R., Otto S. A., Tersmette M., Heeney J. L., Miedema F. Lack of T cell dysfunction and programmed cell death in human immunodeficiency virus type 1-infected chimpanzees correlates with absence of monocytotropic variants. J Infect Dis. 1993 Nov;168(5):1140–1147. doi: 10.1093/infdis/168.5.1140. [DOI] [PubMed] [Google Scholar]
- Shibata R., Hoggan M. D., Broscius C., Englund G., Theodore T. S., Buckler-White A., Arthur L. O., Israel Z., Schultz A., Lane H. C. Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. J Virol. 1995 Jul;69(7):4453–4462. doi: 10.1128/jvi.69.7.4453-4462.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shioda T., Levy J. A., Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
- Theodore T. S., Englund G., Buckler-White A., Buckler C. E., Martin M. A., Peden K. W. Construction and characterization of a stable full-length macrophage-tropic HIV type 1 molecular clone that directs the production of high titers of progeny virions. AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):191–194. doi: 10.1089/aid.1996.12.191. [DOI] [PubMed] [Google Scholar]
- Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Theodore T. S., Martin M. A. Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop that change viral tropism also alter physical and functional properties of the virion envelope. J Virol. 1994 Jul;68(7):4409–4419. doi: 10.1128/jvi.68.7.4409-4419.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wyatt R., Thali M., Tilley S., Pinter A., Posner M., Ho D., Robinson J., Sodroski J. Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. J Virol. 1992 Dec;66(12):6997–7004. doi: 10.1128/jvi.66.12.6997-7004.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]