Relationship Between the V3 Loop and the Phenotypes of Human Immunodeficiency Virus Type 1 (HIV-1) Isolates from Children Perinatally Infected with HIV-1

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1995 Jan 1

PMID 7527089

Citations 10

Authors

F Mammano

F Salvatori

L Ometto

M Panozzo

L Chieco-Bianchi

A De Rossi

Affiliations

Soon will be listed here.

Abstract

The third variable region (V3) of the envelope protein of human immunodeficiency virus type 1 (HIV-1) contains group- and type-specific epitopes for neutralizing antibodies and contains determinants involved in viral tropism and syncytium-inducing (SI) activity. We studied the in vivo relationship between V3 sequences and viral phenotypes in 24 perinatally HIV-1-infected children. To avoid in vitro selection of intrapatient minor variants, genetic studies were performed directly on uncultured peripheral blood mononuclear cells (PBMC), and the tropisms of HIV-1 isolates were evaluated by culturing patients' PBMC directly with monocyte-derived macrophages, lymphocytes, and MT-2 cells. According to their phenotypes, we could define five types of primary isolates: (i) non-syncytium-inducing (NSI) macrophagetropic, (ii) NSI macrophage-lymphotropic, (iii) NSI lymphotropic, (iv) SI lympho-T-cell line-tropic, and (v) SI pleiotropic. The SI viral phenotype was correlated with a more advanced status of disease. Genetic analysis of intrapatient molecular variants revealed that no relationship between the degree of intrapatient V3 variability and the pattern of viral tropism existed; moreover, within a single patient, the values for V3 variability between CD4+ lymphocytes and CD14+ monocytes were similar, thus suggesting that in vivo variability of the monocytotropic variants is more extensive than previously appreciated. A comparison between the intrapatient major variants and the phenotype of primary isolates disclosed that a negatively charged amino acid at residue site 25 was associated with an NSI macrophage- and macrophage-lymphotropic viral phenotype. Finally, by comparing the V3 sequences derived from our study population with those of several prototypes, we observed that the majority of isolates circulating in Italy are related to the North American subtype B macrophagetropic isolates.

Citing Articles

Inhibition of dual/mixed tropic HIV-1 isolates by CCR5-inhibitors in primary lymphocytes and macrophages.

Surdo M, Balestra E, Saccomandi P, Di Santo F, Montano M, Di Carlo D PLoS One. 2013; 8(7):e68076.

PMID: 23874501 PMC: 3706609. DOI: 10.1371/journal.pone.0068076.

Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example.

Buonaguro L, Tagliamonte M, Tornesello M, Buonaguro F Retrovirology. 2007; 4:34.

PMID: 17517125 PMC: 1892567. DOI: 10.1186/1742-4690-4-34.

Characterisation of near-full length genome sequences of three South African human immunodeficiency virus type 1 subtype C isolates.

Hunt G, Papathanasopoulos M, Gray G, Tiemessen C Virus Genes. 2003; 26(1):49-56.

PMID: 12680693 DOI: 10.1023/a:1022378022104.

Expanded tropism of primary human immunodeficiency virus type 1 R5 strains to CD4(+) T-cell lines determined by the capacity to exploit low concentrations of CCR5.

Dejucq N, Simmons G, Clapham P J Virol. 1999; 73(9):7842-7.

PMID: 10438877 PMC: 104314. DOI: 10.1128/JVI.73.9.7842-7847.1999.

Determinant in human immunodeficiency virus type 1 for efficient replication under cytokine-induced CD4(+) T-helper 1 (Th1)- and Th2-type conditions.

Suzuki Y, Koyanagi Y, Tanaka Y, Murakami T, Misawa N, Maeda N J Virol. 1998; 73(1):316-24.

PMID: 9847335 PMC: 103836. DOI: 10.1128/JVI.73.1.316-324.1999.

References

Starcich B, Hahn B, Shaw G, McNeely P, Modrow S, Wolf H . Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986; 45(5):637-48. DOI: 10.1016/0092-8674(86)90778-6. View

Kuiken C, de Jong J, Baan E, Keulen W, Tersmette M, Goudsmit J . Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. J Virol. 1992; 66(7):4622-7. PMC: 241280. DOI: 10.1128/JVI.66.7.4622-4627.1992. View

Folks T, Powell D, Lightfoote M, Koenig S, Fauci A, Benn S . Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986; 164(1):280-90. PMC: 2188205. DOI: 10.1084/jem.164.1.280. View

Scarlatti G, Leitner T, Halapi E, Wahlberg J, Marchisio P, Wigzell H . Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc Natl Acad Sci U S A. 1993; 90(5):1721-5. PMC: 45951. DOI: 10.1073/pnas.90.5.1721. View

de Jong J, de Ronde A, Keulen W, Tersmette M, Goudsmit J . Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. J Virol. 1992; 66(11):6777-80. PMC: 240176. DOI: 10.1128/JVI.66.11.6777-6780.1992. View

Boyd M, Simpson G, Cann A, Johnson M, Weiss R . A single amino acid substitution in the V1 loop of human immunodeficiency virus type 1 gp120 alters cellular tropism. J Virol. 1993; 67(6):3649-52. PMC: 237718. DOI: 10.1128/JVI.67.6.3649-3652.1993. View

Skinner M, Langlois A, McDanal C, McDougal J, Bolognesi D, Matthews T . Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988; 62(11):4195-200. PMC: 253851. DOI: 10.1128/JVI.62.11.4195-4200.1988. View

De Rossi A, Ometto L, Roncella S, DAndrea E, Menin C, Calderazzo F . HIV-1 induces down-regulation of bcl-2 expression and death by apoptosis of EBV-immortalized B cells: a model for a persistent "self-limiting" HIV-1 infection. Virology. 1994; 198(1):234-44. DOI: 10.1006/viro.1994.1026. View

Schwartz S, Felber B, Fenyo E, Pavlakis G . Rapidly and slowly replicating human immunodeficiency virus type 1 isolates can be distinguished according to target-cell tropism in T-cell and monocyte cell lines. Proc Natl Acad Sci U S A. 1989; 86(18):7200-3. PMC: 298024. DOI: 10.1073/pnas.86.18.7200. View

10.

Looney D, Fisher A, Putney S, Rusche J, Redfield R, Burke D . Type-restricted neutralization of molecular clones of human immunodeficiency virus. Science. 1988; 241(4863):357-9. DOI: 10.1126/science.3388046. View

11.

Pang S, Vinters H, Akashi T, OBRIEN W, Chen I . HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J Acquir Immune Defic Syndr (1988). 1991; 4(11):1082-92. View

12.

Fouchier R, Groenink M, Kootstra N, Tersmette M, Huisman H, Miedema F . Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992; 66(5):3183-7. PMC: 241084. DOI: 10.1128/JVI.66.5.3183-3187.1992. View

13.

Andeweg A, Leeflang P, Osterhaus A, Bosch M . Both the V2 and V3 regions of the human immunodeficiency virus type 1 surface glycoprotein functionally interact with other envelope regions in syncytium formation. J Virol. 1993; 67(6):3232-9. PMC: 237663. DOI: 10.1128/JVI.67.6.3232-3239.1993. View

14.

Rusche J, Javaherian K, McDanal C, Petro J, Lynn D, Grimaila R . Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120. Proc Natl Acad Sci U S A. 1988; 85(9):3198-202. PMC: 280171. DOI: 10.1073/pnas.85.9.3198. View

15.

Koot M, Keet I, Vos A, de Goede R, Roos M, Coutinho R . Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993; 118(9):681-8. DOI: 10.7326/0003-4819-118-9-199305010-00004. View

16.

Simmonds P, Balfe P, Peutherer J, Ludlam C, Bishop J, Brown A . Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990; 64(2):864-72. PMC: 249182. DOI: 10.1128/JVI.64.2.864-872.1990. View

17.

Saiki R, Scharf S, Faloona F, Mullis K, Horn G, Erlich H . Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985; 230(4732):1350-4. DOI: 10.1126/science.2999980. View

18.

Emini E, Schleif W, Nunberg J, Conley A, Eda Y, Tokiyoshi S . Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992; 355(6362):728-30. DOI: 10.1038/355728a0. View

19.

Piatak Jr M, Saag M, Yang L, Clark S, Kappes J, Luk K . High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993; 259(5102):1749-54. DOI: 10.1126/science.8096089. View

20.

Tersmette M, Gruters R, de Wolf F, de Goede R, Lange J, Schellekens P . Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989; 63(5):2118-25. PMC: 250628. DOI: 10.1128/JVI.63.5.2118-2125.1989. View