PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
 
J Virol. 1996 December; 70(12): 8355–8360.
PMCID: PMC190923

Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry.

Abstract

A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection of blood-derived macrophages. Infectivity titers for C8166 cells and macrophages demonstrated that primary SI strains infected macrophages much more efficiently than T-cell line-adapted HIV-1 strains such as LAI and RF. These primary SI strains were therefore dual-tropic. Nine biological clones of two SI strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those of their parental viruses, indicating that the dual-tropic phenotype was not due to a mixture of non-SI/macrophage-tropic and SI/T-cell tropic viruses. We tested whether the primary SI strains used either Lestr (fusin) or CCR5 as coreceptors. Infection of cat CCC/CD4 cells transiently expressing Lestr supported infection by T-cell line-adapted strains including LAI, whereas CCC/CD4 cells expressing CCR5 were sensitive to primary non-SI strains as well as to the molecularly cloned strains SF-162 and JR-CSF. Several primary SI strains, as well as the molecularly cloned dual-tropic viruses 89.6 and GUN-1, infected both Lestr+ and CCR5+ CCC/CD4 cells. Thus, these viruses can choose between Lestr and CCR5 for entry into cells. Interestingly, some dual-tropic primary SI strains that infected Lestr+ cells failed to infect CCR5+ cells, suggesting that these viruses may use an alternative coreceptor for infection of macrophages. Alternatively, CCR5 may be processed or presented differently on cat cells so that entry of some primary SI strains but not others is affected.

Full Text

The Full Text of this article is available as a PDF (225K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996 Jun 28;272(5270):1955–1958. [PubMed]
  • Asjö B, Morfeldt-Månson L, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyö EM. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660–662. [PubMed]
  • Chaudhuri A, Zbrzezna V, Polyakova J, Pogo AO, Hesselgesser J, Horuk R. Expression of the Duffy antigen in K562 cells. Evidence that it is the human erythrocyte chemokine receptor. J Biol Chem. 1994 Mar 18;269(11):7835–7838. [PubMed]
  • Cheng-Mayer C, Weiss C, Seto D, Levy JA. Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8575–8579. [PubMed]
  • Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, et al. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28;85(7):1135–1148. [PubMed]
  • Clapham PR, Blanc D, Weiss RA. Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by Simian immunodeficiency virus. Virology. 1991 Apr;181(2):703–715. [PubMed]
  • Clapham PR, McKnight A, Weiss RA. Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4. J Virol. 1992 Jun;66(6):3531–3537. [PMC free article] [PubMed]
  • Clapham PR, Weiss RA, Dalgleish AG, Exley M, Whitby D, Hogg N. Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester. Virology. 1987 May;158(1):44–51. [PubMed]
  • Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811–1815. [PubMed]
  • Collin M, Illei P, James W, Gordon S. Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements. J Gen Virol. 1994 Jul;75(Pt 7):1597–1603. [PubMed]
  • Collman R, Balliet JW, Gregory SA, Friedman H, Kolson DL, Nathanson N, Srinivasan A. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992 Dec;66(12):7517–7521. [PMC free article] [PubMed]
  • Combadiere C, Ahuja SK, Murphy PM. Cloning and functional expression of a human eosinophil CC chemokine receptor. J Biol Chem. 1995 Jul 14;270(28):16491–16494. [PubMed]
  • Connor RI, Ho DD. Human immunodeficiency virus type 1 variants with increased replicative capacity develop during the asymptomatic stage before disease progression. J Virol. 1994 Jul;68(7):4400–4408. [PMC free article] [PubMed]
  • Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. [PubMed]
  • Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell. 1996 Jun 28;85(7):1149–1158. [PubMed]
  • Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. [PubMed]
  • Federsppiel B, Melhado IG, Duncan AM, Delaney A, Schappert K, Clark-Lewis I, Jirik FR. Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen. Genomics. 1993 Jun;16(3):707–712. [PubMed]
  • Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996 May 10;272(5263):872–877. [PubMed]
  • Herzog H, Hort YJ, Shine J, Selbie LA. Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation. DNA Cell Biol. 1993 Jul-Aug;12(6):465–471. [PubMed]
  • Jazin EE, Yoo H, Blomqvist AG, Yee F, Weng G, Walker MW, Salon J, Larhammar D, Wahlestedt C. A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells. Regul Pept. 1993 Sep 22;47(3):247–258. [PubMed]
  • Koot M, Vos AH, Keet RP, de Goede RE, Dercksen MW, Terpstra FG, Coutinho RA, Miedema F, Tersmette M. HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS. 1992 Jan;6(1):49–54. [PubMed]
  • Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV, Chen IS. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. [PubMed]
  • Loetscher M, Geiser T, O'Reilly T, Zwahlen R, Baggiolini M, Moser B. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem. 1994 Jan 7;269(1):232–237. [PubMed]
  • McKnight A, Clapham PR, Weiss RA. HIV-2 and SIV infection of nonprimate cell lines expressing human CD4: restrictions to replication at distinct stages. Virology. 1994 May 15;201(1):8–18. [PubMed]
  • McKnight A, Weiss RA, Shotton C, Takeuchi Y, Hoshino H, Clapham PR. Change in tropism upon immune escape by human immunodeficiency virus. J Virol. 1995 May;69(5):3167–3170. [PMC free article] [PubMed]
  • Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nagata K, Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. [PubMed]
  • Nara PL, Fischinger PJ. Quantitative infectivity assay for HIV-1 and-2. Nature. 1988 Mar 31;332(6163):469–470. [PubMed]
  • Neote K, DiGregorio D, Mak JY, Horuk R, Schall TJ. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell. 1993 Feb 12;72(3):415–425. [PubMed]
  • Nomura H, Nielsen BW, Matsushima K. Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. Int Immunol. 1993 Oct;5(10):1239–1249. [PubMed]
  • Paxton WA, Martin SR, Tse D, O'Brien TR, Skurnick J, VanDevanter NL, Padian N, Braun JF, Kotler DP, Wolinsky SM, et al. Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure. Nat Med. 1996 Apr;2(4):412–417. [PubMed]
  • Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. [PubMed]
  • Power CA, Meyer A, Nemeth K, Bacon KB, Hoogewerf AJ, Proudfoot AE, Wells TN. Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line. J Biol Chem. 1995 Aug 18;270(33):19495–19500. [PubMed]
  • Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem. 1996 Jul 19;271(29):17161–17166. [PubMed]
  • Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996 Mar 19;35(11):3362–3367. [PubMed]
  • Simmons G, McKnight A, Takeuchi Y, Hoshino H, Clapham PR. Cell-to-cell fusion, but not virus entry in macrophages by T-cell line tropic HIV-1 strains: a V3 loop-determined restriction. Virology. 1995 Jun 1;209(2):696–700. [PubMed]
  • Takeuchi Y, Akutsu M, Murayama K, Shimizu N, Hoshino H. Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. J Virol. 1991 Apr;65(4):1710–1718. [PMC free article] [PubMed]
  • Tersmette M, de Goede RE, Al BJ, Winkel IN, Gruters RA, Cuypers HT, Huisman HG, Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. [PMC free article] [PubMed]
  • Valentin A, Albert J, Fenyö EM, Asjö B. Dual tropism for macrophages and lymphocytes is a common feature of primary human immunodeficiency virus type 1 and 2 isolates. J Virol. 1994 Oct;68(10):6684–6689. [PMC free article] [PubMed]
  • Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guétard D, et al. LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science. 1991 May 17;252(5008):961–965. [PubMed]
  • Weiss RA, Clapham PR. Hot fusion of HIV. Nature. 1996 Jun 20;381(6584):647–648. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)