Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Nov;71(11):8582–8591. doi: 10.1128/jvi.71.11.8582-8591.1997

Immunoglobulin V(H) usage during primary infection of rhesus monkeys with chimeric simian-human immunodeficiency viruses.

D H Margolin 1, K A Reimann 1, J Sodroski 1, G B Karlsson 1, K Tenner-Racz 1, P Racz 1, N L Letvin 1
PMCID: PMC192322  PMID: 9343216

Abstract

It has been suggested that naive immunoglobulins encoded by the V(H)3 gene family interact aberrantly with human immunodeficiency virus type 1 (HIV-1) gp120 via a superantigenic epitope, causing initial expansion and eventual depletion of V(H)3-expressing B cells. However, this possibility has not been prospectively assessed during an AIDS virus infection. We determined V(H) family usage in rhesus monkeys during primary infection with chimeric viruses expressing HIV-1 envelopes on a simian immunodeficiency virus (SIVmac) backbone (SHIVs). Four SHIVs with different envelopes and pathogenicities were studied. V(H) family usage was prospectively assessed in peripheral blood mononuclear cells and lymph node cells of these monkeys by a semiquantitative PCR technique. In the first months following SHIV infection, a period of intense viral antigenemia, representation of various V(H) families increased or decreased for individual monkeys, but no single V(H) family was consistently altered. In particular, the average representation of V(H)3-bearing B lymphocytes did not change. This observation suggests that the envelope glycoprotein of HIV-1 does not selectively expand or deplete the V(H)3 repertoire of primate B cells during acute AIDS virus infection, contrary to predictions of the gp120 superantigen hypothesis.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amariglio N., Vonsover A., Hakim I., Neumann Y., Mark Z., Brok-Simoni F., Ben-Bassat I., Rechavi G. Immunoglobulin VH3-positive AIDS-related Burkitt's lymphoma: a possible role for the HIV gp120 superantigen. Acta Haematol. 1994;91(2):103–105. doi: 10.1159/000204265. [DOI] [PubMed] [Google Scholar]
  2. Andris J. S., Capra J. D. The molecular structure of human antibodies specific for the human immunodeficiency virus. J Clin Immunol. 1995 Jan;15(1):17–26. doi: 10.1007/BF01489486. [DOI] [PubMed] [Google Scholar]
  3. Ballet J. J., Sulcebe G., Couderc L. J., Danon F., Rabian C., Lathrop M., Clauvel J. P., Seligmann M. Impaired anti-pneumococcal antibody response in patients with AIDS-related persistent generalized lymphadenopathy. Clin Exp Immunol. 1987 Jun;68(3):479–487. [PMC free article] [PubMed] [Google Scholar]
  4. Berberian L., Goodglick L., Kipps T. J., Braun J. Immunoglobulin VH3 gene products: natural ligands for HIV gp120. Science. 1993 Sep 17;261(5128):1588–1591. doi: 10.1126/science.7690497. [DOI] [PubMed] [Google Scholar]
  5. Berberian L., Shukla J., Jefferis R., Braun J. Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo. J Acquir Immune Defic Syndr. 1994 Jul;7(7):641–646. [PubMed] [Google Scholar]
  6. Berberian L., Valles-Ayoub Y., Sun N., Martinez-Maza O., Braun J. A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest. Blood. 1991 Jul 1;78(1):175–179. [PubMed] [Google Scholar]
  7. Campbell M. J., Zelenetz A. D., Levy S., Levy R. Use of family specific leader region primers for PCR amplification of the human heavy chain variable region gene repertoire. Mol Immunol. 1992 Feb;29(2):193–203. doi: 10.1016/0161-5890(92)90100-c. [DOI] [PubMed] [Google Scholar]
  8. Cattoretti G., Becker M. H., Key G., Duchrow M., Schlüter C., Galle J., Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992 Dec;168(4):357–363. doi: 10.1002/path.1711680404. [DOI] [PubMed] [Google Scholar]
  9. Collman R., Balliet J. W., Gregory S. A., Friedman H., Kolson D. L., 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. doi: 10.1128/jvi.66.12.7517-7521.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  11. David D., Demaison C., Bani L., Thèze J. Progressive decrease in VH3 gene family expression in plasma cells of HIV-infected patients. Int Immunol. 1996 Aug;8(8):1329–1333. doi: 10.1093/intimm/8.8.1329. [DOI] [PubMed] [Google Scholar]
  12. David D., Demaison C., Bani L., Zouali M., Thèze J. Selective variations in vivo of VH3 and VH1 gene family expression in peripheral B cell IgM, IgD and IgG during HIV infection. Eur J Immunol. 1995 Jun;25(6):1524–1528. doi: 10.1002/eji.1830250608. [DOI] [PubMed] [Google Scholar]
  13. Deane M., Norton J. D. Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias. Eur J Immunol. 1990 Oct;20(10):2209–2217. doi: 10.1002/eji.1830201009. [DOI] [PubMed] [Google Scholar]
  14. Fumoux F., Guigou V., Blaise D., Maraninchi D., Fougereau M., Schiff C. Reconstitution of human immunoglobulin VH repertoire after bone marrow transplantation mimics B-cell ontogeny. Blood. 1993 Jun 1;81(11):3153–3157. [PubMed] [Google Scholar]
  15. Goodglick L., Zevit N., Neshat M. S., Braun J. Mapping the Ig superantigen-binding site of HIV-1 gp120. J Immunol. 1995 Dec 1;155(11):5151–5159. [PubMed] [Google Scholar]
  16. Huang C., Stewart A. K., Schwartz R. S., Stollar B. D. Immunoglobulin heavy chain gene expression in peripheral blood B lymphocytes. J Clin Invest. 1992 Apr;89(4):1331–1343. doi: 10.1172/JCI115719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karlsson G. B., Halloran M., Li J., Park I. W., Gomila R., Reimann K. A., Axthelm M. K., Iliff S. A., Letvin N. L., Sodroski J. Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol. 1997 Jun;71(6):4218–4225. doi: 10.1128/jvi.71.6.4218-4225.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karray S., Zouali M. Identification of the B cell superantigen-binding site of HIV-1 gp120. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1356–1360. doi: 10.1073/pnas.94.4.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kohsaka H., Carson D. A., Rassenti L. Z., Ollier W. E., Chen P. P., Kipps T. J., Miyasaka N. The human immunoglobulin V(H) gene repertoire is genetically controlled and unaltered by chronic autoimmune stimulation. J Clin Invest. 1996 Dec 15;98(12):2794–2800. doi: 10.1172/JCI119106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kraj P., Friedman D. F., Stevenson F., Silberstein L. E. Evidence for the overexpression of the VH4-34 (VH4.21) Ig gene segment in the normal adult human peripheral blood B cell repertoire. J Immunol. 1995 Jun 15;154(12):6406–6420. [PubMed] [Google Scholar]
  21. Letvin N. L., King N. W. Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Acquir Immune Defic Syndr. 1990;3(11):1023–1040. [PubMed] [Google Scholar]
  22. Miedema F., Petit A. J., Terpstra F. G., Schattenkerk J. K., de Wolf F., Al B. J., Roos M., Lange J. M., Danner S. A., Goudsmit J. Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs. J Clin Invest. 1988 Dec;82(6):1908–1914. doi: 10.1172/JCI113809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Müller S., Margolin D. H., Min G. An HIV-1 infection-related idiotype/clonotype (1F7) is expressed on antibodies directed to envelope glycoprotein in simian immunodeficiency virus- and chimeric simian/human immunodeficiency virus-infected rhesus monkeys. Hybridoma. 1997 Feb;16(1):17–21. doi: 10.1089/hyb.1997.16.17. [DOI] [PubMed] [Google Scholar]
  24. Müller S., Wang H. T., Kaveri S. V., Chattopadhyay S., Köhler H. Generation and specificity of monoclonal anti-idiotypic antibodies against human HIV-specific antibodies. I. Cross-reacting idiotopes are expressed in subpopulations of HIV-infected individuals. J Immunol. 1991 Aug 1;147(3):933–941. [PubMed] [Google Scholar]
  25. Müller S., Wang H., Silverman G. J., Bramlet G., Haigwood N., Köhler H. B-cell abnormalities in AIDS: stable and clonally-restricted antibody response in HIV-1 infection. Scand J Immunol. 1993 Oct;38(4):327–334. doi: 10.1111/j.1365-3083.1993.tb01734.x. [DOI] [PubMed] [Google Scholar]
  26. Newman R., Alberts J., Anderson D., Carner K., Heard C., Norton F., Raab R., Reff M., Shuey S., Hanna N. "Primatization" of recombinant antibodies for immunotherapy of human diseases: a macaque/human chimeric antibody against human CD4. Biotechnology (N Y) 1992 Nov;10(11):1455–1460. doi: 10.1038/nbt1192-1455. [DOI] [PubMed] [Google Scholar]
  27. Norton A. J., Jordan S., Yeomans P. Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues. J Pathol. 1994 Aug;173(4):371–379. doi: 10.1002/path.1711730413. [DOI] [PubMed] [Google Scholar]
  28. Ratner L., Fisher A., Jagodzinski L. L., Mitsuya H., Liou R. S., Gallo R. C., Wong-Staal F. Complete nucleotide sequences of functional clones of the AIDS virus. AIDS Res Hum Retroviruses. 1987 Spring;3(1):57–69. doi: 10.1089/aid.1987.3.57. [DOI] [PubMed] [Google Scholar]
  29. Regier D. A., Desrosiers R. C. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. doi: 10.1089/aid.1990.6.1221. [DOI] [PubMed] [Google Scholar]
  30. Reimann K. A., Li J. T., Veazey R., Halloran M., Park I. W., Karlsson G. B., Sodroski J., Letvin N. L. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J Virol. 1996 Oct;70(10):6922–6928. doi: 10.1128/jvi.70.10.6922-6928.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Reimann K. A., Li J. T., Voss G., Lekutis C., Tenner-Racz K., Racz P., Lin W., Montefiori D. C., Lee-Parritz D. E., Lu Y. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. J Virol. 1996 May;70(5):3198–3206. doi: 10.1128/jvi.70.5.3198-3206.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reimann K. A., Snyder G. B., Chalifoux L. V., Waite B. C., Miller M. D., Yamamoto H., Spertini O., Letvin N. L. An activated CD8+ lymphocyte appears in lymph nodes of rhesus monkeys early after infection with simian immunodeficiency virus. J Clin Invest. 1991 Oct;88(4):1113–1120. doi: 10.1172/JCI115410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Reimann K. A., Tenner-Racz K., Racz P., Montefiori D. C., Yasutomi Y., Lin W., Ransil B. J., Letvin N. L. Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Virol. 1994 Apr;68(4):2362–2370. doi: 10.1128/jvi.68.4.2362-2370.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Reimann K. A., Waite B. C., Lee-Parritz D. E., Lin W., Uchanska-Ziegler B., O'Connell M. J., Letvin N. L. Use of human leukocyte-specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys. Cytometry. 1994 Sep 1;17(1):102–108. doi: 10.1002/cyto.990170113. [DOI] [PubMed] [Google Scholar]
  35. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  36. Shirai A., Cosentino M., Leitman-Klinman S. F., Klinman D. M. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J Clin Invest. 1992 Feb;89(2):561–566. doi: 10.1172/JCI115621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Terpstra F. G., Al B. J., Roos M. T., De Wolf F., Goudsmit J., Schellekens P. T., Miedema F. Longitudinal study of leukocyte functions in homosexual men seroconverted for HIV: rapid and persistent loss of B cell function after HIV infection. Eur J Immunol. 1989 Apr;19(4):667–673. doi: 10.1002/eji.1830190415. [DOI] [PubMed] [Google Scholar]
  38. Townsley-Fuchs J., Neshat M. S., Margolin D. H., Braun J., Goodglick L. HIV-1 gp120: a novel viral B cell superantigen. Int Rev Immunol. 1997;14(4):325–338. doi: 10.3109/08830189709116523. [DOI] [PubMed] [Google Scholar]

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

RESOURCES