Search tips
Search criteria 


Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1994 September; 68(9): 5395–5402.
PMCID: PMC236939

Effects of natural sequence variation on recognition by monoclonal antibodies neutralize simian immunodeficiency virus infectivity.


The determinants of immune recognition by five monoclonal antibodies (KK5, KK9, KK17, Senv7.1, and Senv101.1) that neutralize simian immunodeficiency virus infectivity were analyzed. These five neutralizing monoclonal antibodies were generated to native SIVmac251 envelope glycoprotein expressed by a vaccinia virus recombinant vector. All five recognize conformational or discontinuous epitopes and require native antigen for optimal recognition. These monoclonal antibodies also recognize SIVmac239 gp120, but they do not recognize gp120 of two natural variants of SIVmac239, 1-12 and 8-22, which evolved during the course of persistent infection in vivo (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843-1854, 1991). Recombinant viruses which were constructed by exchanging variable regions between SIVmac239 and variant 1-12 were used to define domains important for recognition. Radioimmunoprecipitation analysis demonstrated that sequence changes in variable regions 4 and 5 (V4/V5) were primarily responsible for the loss of recognition of the 1-12 variant. Site-specific mutants were used to define precise changes that eliminate recognition by these neutralizing antibodies. Changing N-409 to D, deletion of KPKE, and deletion of KEQH in V4 each resulted in loss of recognition by all five monoclonal antibodies. SIVs with these natural sequence changes are still replication competent and viable. Changing A-417 to T or A/N-417/418 to TK in V4 or Q-477 to K in V5 did not alter recognition detectably. These results define specific, naturally occurring sequence changes in V4 of SIVmac that result in loss of recognition by one class of SIVmac neutralizing antibodies.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Albert J, Abrahamsson B, Nagy K, Aurelius E, Gaines H, Nyström G, Fenyö EM. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS. 1990 Feb;4(2):107–112. [PubMed]
  • Benichou S, Legrand R, Nakagawa N, Faure T, Traincard F, Vogt G, Dormont D, Tiollais P, Kieny MP, Madaule P. Identification of a neutralizing domain in the external envelope glycoprotein of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1165–1170. [PubMed]
  • Berkower I, Murphy D, Smith CC, Smith GE. A predominant group-specific neutralizing epitope of human immunodeficiency virus type 1 maps to residues 342 to 511 of the envelope glycoprotein gp120. J Virol. 1991 Nov;65(11):5983–5990. [PMC free article] [PubMed]
  • Burns DP, Collignon C, Desrosiers RC. Simian immunodeficiency virus mutants resistant to serum neutralization arise during persistent infection of rhesus monkeys. J Virol. 1993 Jul;67(7):4104–4113. [PMC free article] [PubMed]
  • Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosiers RC, Tiollais P, Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. [PubMed]
  • Cheevers WP, Knowles DP, Jr, Norton LK. Neutralization-resistant antigenic variants of caprine arthritis-encephalitis lentivirus associated with progressive arthritis. J Infect Dis. 1991 Oct;164(4):679–685. [PubMed]
  • Daniel MD, Letvin NL, King NW, Kannagi M, Sehgal PK, Hunt RD, Kanki PJ, Essex M, Desrosiers RC. Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science. 1985 Jun 7;228(4704):1201–1204. [PubMed]
  • di Marzo Veronese F, Reitz MS, Jr, Gupta G, Robert-Guroff M, Boyer-Thompson C, Louie A, Gallo RC, Lusso P. Loss of a neutralizing epitope by a spontaneous point mutation in the V3 loop of HIV-1 isolated from an infected laboratory worker. J Biol Chem. 1993 Dec 5;268(34):25894–25901. [PubMed]
  • D'Souza MP, Kent KA, Thiriart C, Collignon C, Milman G. International collaboration comparing neutralization and binding assays for monoclonal antibodies to simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1993 May;9(5):415–422. [PubMed]
  • Ellis TM, Wilcox GE, Robinson WF. Antigenic variation of caprine arthritis-encephalitis virus during persistent infection of goats. J Gen Virol. 1987 Dec;68(Pt 12):3145–3152. [PubMed]
  • Ho SN, Hunt HD, Horton RM, Pullen JK, Pease LR. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. [PubMed]
  • Javaherian K, Langlois AJ, Montefiori DC, Kent KA, Ryan KA, Wyman PD, Stott J, Bolognesi DP, Murphey-Corb M, Larosa GJ. Studies of the conformation-dependent neutralizing epitopes of simian immunodeficiency virus envelope protein. J Virol. 1994 Apr;68(4):2624–2631. [PMC free article] [PubMed]
  • Javaherian K, Langlois AJ, Schmidt S, Kaufmann M, Cates N, Langedijk JP, Meloen RH, Desrosiers RC, Burns DP, Bolognesi DP, et al. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1418–1422. [PubMed]
  • Johnson PR, Hamm TE, Goldstein S, Kitov S, Hirsch VM. The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques. Virology. 1991 Nov;185(1):217–228. [PubMed]
  • Kent KA, Gritz L, Stallard G, Cranage MP, Collignon C, Thiriart C, Corcoran T, Silvera P, Stott EJ. Production and of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins. AIDS. 1991 Jul;5(7):829–836. [PubMed]
  • Kent KA, Rud E, Corcoran T, Powell C, Thiriart C, Collignon C, Stott EJ. Identification of two neutralizing and 8 non-neutralizing epitopes on simian immunodeficiency virus envelope using monoclonal antibodies. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1147–1151. [PubMed]
  • Kestler H, Kodama T, Ringler D, Marthas M, Pedersen N, Lackner A, Regier D, Sehgal P, Daniel M, King N, et al. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. [PubMed]
  • Kodama T, Burns DP, Silva DP, Veronese FD, Desrosiers RC. Strain-specific neutralizing determinant in the transmembrane protein of simian immunodeficiency virus. J Virol. 1991 Apr;65(4):2010–2018. [PMC free article] [PubMed]
  • Kono Y. Antigenic variation of equine infectious anemia virus as detected by virus neutralization. Brief report. Arch Virol. 1988;98(1-2):91–97. [PubMed]
  • Kono Y, Kobayashi K, Fukunaga Y. Antigenic drift of equine infectious anemia virus in chronically infected horses. Arch Gesamte Virusforsch. 1973;41(1):1–10. [PubMed]
  • Lutley R, Pétursson G, Pálsson PA, Georgsson G, Klein J, Nathanson N. Antigenic drift in visna: virus variation during long-term infection of Icelandic sheep. J Gen Virol. 1983 Jul;64(Pt 7):1433–1440. [PubMed]
  • McBride BW, Corthals G, Rud E, Kent K, Webster S, Cook N, Cranage MP. Comparison of serum antibody reactivities to a conformational and to linear antigenic sites in the external envelope glycoprotein of simian immunodeficiency virus (SIVmac) induced by infection and vaccination. J Gen Virol. 1993 Jun;74(Pt 6):1033–1041. [PubMed]
  • McGuire TC, Norton LK, O'Rourke KI, Cheevers WP. Antigenic variation of neutralization-sensitive epitopes of caprine arthritis-encephalitis lentivirus during persistent arthritis. J Virol. 1988 Sep;62(9):3488–3492. [PMC free article] [PubMed]
  • Montelaro RC, Parekh B, Orrego A, Issel CJ. Antigenic variation during persistent infection by equine infectious anemia virus, a retrovirus. J Biol Chem. 1984 Aug 25;259(16):10539–10544. [PubMed]
  • Moore JP, Ho DD. Antibodies to discontinuous or conformationally sensitive epitopes on the gp120 glycoprotein of human immunodeficiency virus type 1 are highly prevalent in sera of infected humans. J Virol. 1993 Feb;67(2):863–875. [PMC free article] [PubMed]
  • Moore JP, Nara PL. The role of the V3 loop of gp120 in HIV infection. AIDS. 1991;5 (Suppl 2):S21–S33. [PubMed]
  • Moore JP, Sattentau QJ, Wyatt R, Sodroski J. Probing the structure of the human immunodeficiency virus surface glycoprotein gp120 with a panel of monoclonal antibodies. J Virol. 1994 Jan;68(1):469–484. [PMC free article] [PubMed]
  • Naidu YM, Kestler HW, 3rd, Li Y, Butler CV, Silva DP, Schmidt DK, Troup CD, Sehgal PK, Sonigo P, Daniel MD, et al. Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol. 1988 Dec;62(12):4691–4696. [PMC free article] [PubMed]
  • Narayan O, Griffin DE, Clements JE. Virus mutation during 'slow infection': temporal development and characterization of mutants of visna virus recovered from sheep. J Gen Virol. 1978 Nov;41(2):343–352. [PubMed]
  • Overbaugh J, Rudensey LM, Papenhausen MD, Benveniste RE, Morton WR. Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS. J Virol. 1991 Dec;65(12):7025–7031. [PMC free article] [PubMed]
  • Regier DA, Desrosiers RC. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. [PubMed]
  • Steimer KS, Klasse PJ, McKeating JA. HIV-1 neutralization directed to epitopes other than linear V3 determinants. AIDS. 1991;5 (Suppl 2):S135–S143. [PubMed]
  • Steimer KS, Scandella CJ, Skiles PV, Haigwood NL. Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120. Science. 1991 Oct 4;254(5028):105–108. [PubMed]
  • Torres JV, Malley A, Banapour B, Anderson DE, Axthelm MK, Gardner MB, Benjamini E. An epitope on the surface envelope glycoprotein (gp130) of simian immunodeficiency virus (SIVmac) involved in viral neutralization and T cell activation. AIDS Res Hum Retroviruses. 1993 May;9(5):423–430. [PubMed]
  • Tremblay M, Wainberg MA. Neutralization of multiple HIV-1 isolates from a single subject by autologous sequential sera. J Infect Dis. 1990 Sep;162(3):735–737. [PubMed]

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