Home LiteratureArticle Details
PMID: 15452240 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1.

Journal of virology ·Vol. 78 ·No. 20 ·2004-10-00 ·Pages 11208-18

Ritola K, Pilcher CD, Fiscus SA, Hoffman NG, Nelson JA, Kitrinos KM, Hicks CB, Eron JJ, Swanstrom R

Abstract

Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is a low-probability event in which there is thought to be low genetic complexity in the initial inoculum. In order to assess the viral complexity present during primary HIV-1 infection, the V1/V2 and V3 variable regions of the env gene were examined by using a heteroduplex tracking assay (HTA) capable of resolving these genotypic variants. Blood plasma samples from 26 primary HIV-1-infected subjects were analyzed for their level of diversity. Half of the subjects had more than one V1/V2 viral variant during primary infection, indicating the frequent transmission of multiple variants. This observation is inconsistent with the idea of infrequent transmission based on a small transmitting inoculum of cell-free virus. In chronically infected subjects, the complexity of the viral populations was even greater in both the V1/V2 and the V3 regions than in acutely infected subjects, indicating that in spite of the presence of multiple variants in acute infection, the virus does pass through a genetic bottleneck during transmission. We also examined how well the infecting virus penetrated different anatomical compartments by using the HTA. Viral variants detected in blood plasma were compared to those detected in seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each of these compartments was to a large extent identical to virus in blood plasma, a finding consistent with rapid penetration of the infecting variant(s). The low-probability transmission of multiple variants could be the result of transient periods of hyperinfectiousness or hypersusceptibility. Alternatively, the inefficient transfer of a multiply infected cell could account for both the low probability of transmission and the transfer of multiple variants.

MeSH Terms
Acute Disease Cerebrospinal Fluid/virology Cohort Studies Female Gene Products, env/genetics Genetic Variation HIV Infections/virology HIV-1/classification,genetics Heteroduplex Analysis Humans Male Molecular Sequence Data RNA, Viral/blood Semen/virology Sequence Analysis, DNA Viral Load
Chemicals
Gene Products, env RNA, Viral
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Ritola Kimberly
University of North Carolina at Chapel Hill, 22-062 Lineberger Cancer Center, CB 7295, Chapel Hill, NC 27599-7295, USA.
Pilcher Christopher D
Fiscus Susan A
Hoffman Noah G
Nelson Julie A E
Kitrinos Kathryn M
Hicks Charles B
Eron Joseph J
Swanstrom Ronald
References (68)
68 references, click to expand
  1. Rapid evolution of the neutralizing antibody response to HIV type 1 infection.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9 PMID: 12644702
  2. Turnover of env variable region 1 and 2 genotypes in subjects with late-stage human immunodeficiency virus type 1 infection.
    J Virol. 2003 Jun;77(12):6811-22 PMID: 12768001
  3. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.
    AIDS. 2003 Sep 5;17(13):1871-9 PMID: 12960819
  4. Correlation between env V1/V2 region diversification and neutralizing antibodies during primary infection by simian immunodeficiency virus sm in rhesus macaques.
    J Virol. 2004 Apr;78(7):3561-71 PMID: 15016879
  5. Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission.
    Science. 2004 Mar 26;303(5666):2019-22 PMID: 15044802
  6. Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII.
    Lancet. 1985 Aug 3;2(8449):233-6 PMID: 2862416
  7. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection.
    N Engl J Med. 1991 Apr 4;324(14):961-4 PMID: 1823118
  8. Naturally occurring mutations within HIV-1 V3 genomic RNA lead to antigenic variation dependent on a single amino acid substitution.
    Virology. 1991 Nov;185(1):195-205 PMID: 1656585
  9. Genotypic and phenotypic characterization of HIV-1 patients with primary infection.
    Science. 1993 Aug 27;261(5125):1179-81 PMID: 8356453
  10. Genomic human immunodeficiency virus type 1 RNA variation in mother and child following intra-uterine virus transmission.
    J Gen Virol. 1993 Sep;74 ( Pt 9):1747-56 PMID: 8376956
  11. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes.
    Science. 1993 Nov 19;262(5137):1257-61 PMID: 8235655
  12. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.
    J Virol. 1994 Jul;68(7):4650-5 PMID: 8207839
  13. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1.
    J Virol. 1994 Aug;68(8):5142-55 PMID: 8035514
  14. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays.
    J Virol. 1994 Oct;68(10):6672-83 PMID: 8084001
  15. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.
    J Clin Invest. 1994 Nov;94(5):2060-7 PMID: 7962552
  16. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection.
    N Engl J Med. 1995 Jan 26;332(4):201-8 PMID: 7808485
  17. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy.
    Science. 1995 Jan 27;267(5197):483-9 PMID: 7824947
  18. HIV type 1 V3 sequence diversity in contact-traced Swedish couples at the time of sexual transmission.
    AIDS Res Hum Retroviruses. 1994 Sep;10(9):1187-9 PMID: 7826703
  19. Genotypic selection of simian immunodeficiency virus in macaque infants infected transplacentally.
    J Virol. 1995 Dec;69(12):7982-90 PMID: 7494311
  20. Diversity in virus populations from genital secretions and peripheral blood from women recently infected with human immunodeficiency virus type 1.
    J Virol. 1995 Dec;69(12):8118-22 PMID: 7494333
  21. Toward an understanding of the correlates of protective immunity to HIV infection.
    Science. 1996 Jan 19;271(5247):324-8 PMID: 8553066
  22. Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.
    J Virol. 1996 May;70(5):3098-107 PMID: 8627789
  23. Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection.
    Science. 1996 Apr 26;272(5261):537-42 PMID: 8614801
  24. Clinical and epidemiologic features of primary HIV infection.
    Ann Intern Med. 1996 Aug 15;125(4):257-64 PMID: 8678387
  25. Primary infections with HIV-1 of women and their offspring in Rwanda: findings of heterogeneity at seroconversion, coinfection, and recombinants of HIV-1 subtypes A and C.
    Virology. 1997 Jan 6;227(1):63-76 PMID: 9007059
  26. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus.
    Nat Med. 1997 Feb;3(2):205-11 PMID: 9018240
  27. Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.
    Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1396-401 PMID: 9037064
  28. Divergent patterns of progression to AIDS after infection from the same source: human immunodeficiency virus type 1 evolution and antiviral responses.
    J Virol. 1997 Jun;71(6):4284-95 PMID: 9151816
  29. Restriction of viral population by intravaginal infection of simian immunodeficiency viruses in macaque monkeys.
    Arch Virol. 1997;142(1):37-51 PMID: 9155871
  30. Tracking changes in HIV-1 envelope quasispecies using DNA heteroduplex analysis.
    Methods. 1997 Aug;12(4):348-54 PMID: 9245616
  31. Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS.
    J Virol. 1997 Oct;71(10):7498-508 PMID: 9311829
  32. Evolutionary variants of the human immunodeficiency virus type 1 V3 region characterized by using a heteroduplex tracking assay.
    J Virol. 1997 Nov;71(11):8750-8 PMID: 9343234
  33. Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians.
    J Virol. 1997 Nov;71(11):8908-11 PMID: 9343257
  34. A genetic and viral load analysis of the simian immunodeficiency virus during the acute phase in macaques inoculated by the vaginal route.
    AIDS Res Hum Retroviruses. 1998 Jan 20;14(2):171-81 PMID: 9462928
  35. Cross-reactions between the cytotoxic T-lymphocyte responses of human immunodeficiency virus-infected African and European patients.
    J Virol. 1998 May;72(5):3547-53 PMID: 9557634
  36. Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type 1 clade B infection.
    AIDS Res Hum Retroviruses. 1998 Jul 20;14(11):925-37 PMID: 9686639
  37. V3 sequence diversity of HIV-1 subtype E in infected mothers and their infants.
    J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Aug 1;18(4):323-31 PMID: 9704937
  38. Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.
    J Clin Invest. 1998 Nov 1;102(9):1758-65 PMID: 9802890
  39. Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais.
    J Infect Dis. 1998 Oct;178(4):1040-6 PMID: 9806032
  40. Molecular epidemiology of HIV transmission in a dental practice.
    Science. 1992 May 22;256(5060):1165-71 PMID: 1589796
  41. Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection.
    J Virol. 1999 Dec;73(12):10489-502 PMID: 10559367
  42. Gender differences in HIV-1 diversity at time of infection.
    Nat Med. 2000 Jan;6(1):71-5 PMID: 10613827
  43. HIV-1 genomic RNA diversification following sexual and parenteral virus transmission.
    Virology. 1992 Jul;189(1):103-10 PMID: 1376536
  44. Rapid generation of sequence variation during primary HIV-1 infection.
    AIDS. 1992 May;6(5):453-60 PMID: 1616650
  45. Evolution of sequence divergence among human immunodeficiency virus type 1 isolates derived from a blood donor and a recipient.
    Pediatr Res. 1993 Jan;33(1):36-42 PMID: 8433858
  46. 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 Mar 1;90(5):1721-5 PMID: 8446584
  47. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection.
    J Virol. 1993 Jun;67(6):3345-56 PMID: 8497055
  48. Independent variation and positive selection in env V1 and V2 domains within maternal-infant strains of human immunodeficiency virus type 1 in vivo.
    J Virol. 1993 Jul;67(7):3951-60 PMID: 8510212
  49. Patterns of changes in human immunodeficiency virus type 1 V3 sequence populations late in infection.
    J Virol. 2000 Sep;74(18):8494-501 PMID: 10954550
  50. Genetic analysis of viral variants selected in transmission of human immunodeficiency viruses to newborns.
    AIDS Res Hum Retroviruses. 2000 Sep 1;16(13):1223-33 PMID: 10957720
  51. Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen.
    J Virol. 2000 Oct;74(19):8946-52 PMID: 10982338
  52. Viral dynamics in primary HIV-1 infection. Karolinska Institutet Primary HIV Infection Study Group.
    AIDS. 2000 Oct 20;14(15):2283-91 PMID: 11089616
  53. Diagnosis of primary HIV-1 infection. Los Angeles County Primary HIV Infection Recruitment Network.
    Ann Intern Med. 2001 Jan 2;134(1):25-9 PMID: 11187417
  54. A multiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics.
    Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):176-81 PMID: 11120887
  55. Perinatal transmission of major, minor, and multiple maternal human immunodeficiency virus type 1 variants in utero and intrapartum.
    J Virol. 2001 Mar;75(5):2194-203 PMID: 11160723
  56. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model.
    AIDS. 2001 Mar 30;15(5):621-7 PMID: 11317000
  57. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.
    Lancet. 2001 Apr 14;357(9263):1149-53 PMID: 11323041
  58. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa.
    AIDS Res Hum Retroviruses. 2001 Jul 1;17(10):901-10 PMID: 11461676
  59. Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity.
    J Virol. 2001 Nov;75(21):10073-89 PMID: 11581376
  60. Sexual transmission during the incubation period of primary HIV infection.
    JAMA. 2001 Oct 10;286(14):1713-4 PMID: 11594895
  61. Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia.
    J Virol. 2002 Jan;76(1):397-405 PMID: 11739704
  62. Use of the sensitive/less-sensitive (detuned) EIA strategy for targeting genetic analysis of HIV-1 to recently infected blood donors.
    AIDS. 2002 Jan 4;16(1):113-9 PMID: 11741169
  63. The selection and evolution of viral quasispecies in HIV-1 infected children.
    HIV Med. 2002 Jan;3(1):1-11 PMID: 12059945
  64. Recombination: Multiply infected spleen cells in HIV patients.
    Nature. 2002 Jul 11;418(6894):144 PMID: 12110879
  65. Virus population homogenization following acute human immunodeficiency virus type 1 infection.
    J Virol. 2002 Dec;76(23):11953-9 PMID: 12414937
  66. Diversity of the human immunodeficiency virus type 1 (HIV-1) env sequence after vertical transmission in mother-child pairs infected with HIV-1 subtype A.
    J Virol. 2003 Mar;77(5):3050-7 PMID: 12584330
  67. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development.
    AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44 PMID: 12639249
  68. In-utero transmission of quasispecies among human immunodeficiency virus type 1 genotypes.
    Virology. 2003 Mar 15;307(2):278-82 PMID: 12667797
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.78.20.11208-11218.2004
Published
2004-10-00
Pages
11208-18
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC521858
Subset
IM
Grants
NIAID NIH HHS · T32 AI 007419 · United States
NCRR NIH HHS · M01 RR000046 · United States
NIAID NIH HHS · K23 AI 01781 · United States
NIAID NIH HHS · T32 AI007419 · United States
NCRR NIH HHS · RR 00046 · United States
NIAID NIH HHS · K24 AI001608 · United States
NIDDK NIH HHS · R01 DK049381 · United States
NIAID NIH HHS · K23 AI001781 · United States
NIDDK NIH HHS · R01 DK 49381 · United States
NIAID NIH HHS · R01 AI044667 · United States
NIAID NIH HHS · P30 AI 50410 · United States
NIAID NIH HHS · R01 AI 44667 · United States
NIAID NIH HHS · K24 AI 01608 · United States
NIAID NIH HHS · P30 AI050410 · United States
Databases
GENBANK
AY705242, AY705243, AY705244, AY705245, AY705246, AY705247, AY705248, AY705249, AY705250, AY705251, AY705252, AY705253, AY705254, AY705255, AY705256, AY705257, AY705258, AY705259, AY705260, AY705261, AY705262, AY705263, AY705264, AY705265, AY705266, AY705267, AY705268, AY705269, AY705270, AY705271, AY705272, AY705273, AY705274, AY705275, AY705276, AY705277, AY705278, AY705279, AY705280, AY705281, AY705282, AY705283, AY705284, AY705285, AY705286, AY705287, AY705288, AY705289, AY705290, AY705291, AY705292, AY705293, AY705294, AY705295, AY705296, AY705297, AY705298, AY705299, AY705300, AY705301, AY705302, AY705303, AY705304, AY705305, AY705306, AY705307, AY705308, AY705309, AY705310, AY705311, AY705312, AY705313, AY705314, AY705315, AY705316, AY705317, AY705318, AY705319, AY705320, AY705321, AY705322, AY705323, AY705324, AY705325, AY705326, AY705327, AY705328, AY705329, AY705330, AY705331, AY705332, AY705333, AY705334, AY705335, AY705336, AY705337, AY705338, AY705339, AY705340, AY705341, AY705342, AY705343, AY705344, AY705345, AY705346, AY705347, AY705348
External Links
PubMed source DOI: 10.1128/JVI.78.20.11208-11218.2004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2