Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes

Satoshi Komoto, Masanobu Kinomoto, Madiha S. Ibrahim, Qiu Zhong, Wattana Auwanit, Panasda I.N. Ayuthaya, Toru Otake, Haruyo Mori, Isao Oishi, Takeshi Kurosu, Hirokazu Takahashi, Tetsu Mukai, Kazuyoshi Ikuta

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The viral accessory gene product Nef has been shown to play an important role in human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis. Only little information is available regarding the differences in the host immune responses against Nef protein and its function in vivo among different subtypes of HIV-1. In the present study, we showed marked differences in the immune responses to Nef protein between subtypes B and E. The amino acid sequence in subtype E Nef showed 72% homology with that in subtype B. Most murine monoclonal antibodies obtained by immunization with subtype B or E Nef protein showed cross-reactivity with both Nef proteins (80 and 67%, respectively). Next, we focused on the immune responses among infected Japanese and Thai individuals. Subtyping of the individuals into B and E was carried out by enzyme-linked immunosorbent assay (ELISA) using synthetic peptides corresponding to the V3 loop representing the principal neutralizing domain. Most of the sera from these individuals reacted strongly with Gag p24 proteins derived from subtypes B and E at similar levels. However, the immune responses among these individuals to Nef protein were markedly different. Some subtype B-infected Japanese and Thai individuals (40 and 35%, respectively) showed higher levels of anti-Nef antibodies, although these antibodies preferentially recognized epitopes specific to subtype B. On the other hand, most of the subtype E-infected Japanese and Thai individuals showed low or no antibody responses to Nef proteins. Thus, immune responses to Nef were markedly different between subtypes B- and E-infected carriers, suggesting different function(s) for Nef in AIDS pathogenesis. Further, vaccine design must take into account the different subtypes of HIV-1.

Original languageEnglish
Pages (from-to)3019-3032
Number of pages14
JournalVaccine
Volume19
Issue number20-22
DOIs
Publication statusPublished - 06-04-2001

Fingerprint

nef Gene Products
Human immunodeficiency virus 1
epitopes
Antibody Formation
HIV-1
Epitopes
antibodies
Antibodies
immune response
proteins
pathogenesis
gag Gene Products
Viral Proteins
synthetic peptides
Anti-Idiotypic Antibodies
Amino Acid Sequence
Immunization
cross reaction
neutralization
Acquired Immunodeficiency Syndrome

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Komoto, Satoshi ; Kinomoto, Masanobu ; Ibrahim, Madiha S. ; Zhong, Qiu ; Auwanit, Wattana ; Ayuthaya, Panasda I.N. ; Otake, Toru ; Mori, Haruyo ; Oishi, Isao ; Kurosu, Takeshi ; Takahashi, Hirokazu ; Mukai, Tetsu ; Ikuta, Kazuyoshi. / Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes. In: Vaccine. 2001 ; Vol. 19, No. 20-22. pp. 3019-3032.
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title = "Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes",
abstract = "The viral accessory gene product Nef has been shown to play an important role in human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis. Only little information is available regarding the differences in the host immune responses against Nef protein and its function in vivo among different subtypes of HIV-1. In the present study, we showed marked differences in the immune responses to Nef protein between subtypes B and E. The amino acid sequence in subtype E Nef showed 72{\%} homology with that in subtype B. Most murine monoclonal antibodies obtained by immunization with subtype B or E Nef protein showed cross-reactivity with both Nef proteins (80 and 67{\%}, respectively). Next, we focused on the immune responses among infected Japanese and Thai individuals. Subtyping of the individuals into B and E was carried out by enzyme-linked immunosorbent assay (ELISA) using synthetic peptides corresponding to the V3 loop representing the principal neutralizing domain. Most of the sera from these individuals reacted strongly with Gag p24 proteins derived from subtypes B and E at similar levels. However, the immune responses among these individuals to Nef protein were markedly different. Some subtype B-infected Japanese and Thai individuals (40 and 35{\%}, respectively) showed higher levels of anti-Nef antibodies, although these antibodies preferentially recognized epitopes specific to subtype B. On the other hand, most of the subtype E-infected Japanese and Thai individuals showed low or no antibody responses to Nef proteins. Thus, immune responses to Nef were markedly different between subtypes B- and E-infected carriers, suggesting different function(s) for Nef in AIDS pathogenesis. Further, vaccine design must take into account the different subtypes of HIV-1.",
author = "Satoshi Komoto and Masanobu Kinomoto and Ibrahim, {Madiha S.} and Qiu Zhong and Wattana Auwanit and Ayuthaya, {Panasda I.N.} and Toru Otake and Haruyo Mori and Isao Oishi and Takeshi Kurosu and Hirokazu Takahashi and Tetsu Mukai and Kazuyoshi Ikuta",
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Komoto, S, Kinomoto, M, Ibrahim, MS, Zhong, Q, Auwanit, W, Ayuthaya, PIN, Otake, T, Mori, H, Oishi, I, Kurosu, T, Takahashi, H, Mukai, T & Ikuta, K 2001, 'Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes', Vaccine, vol. 19, no. 20-22, pp. 3019-3032. https://doi.org/10.1016/S0264-410X(00)00444-8

Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes. / Komoto, Satoshi; Kinomoto, Masanobu; Ibrahim, Madiha S.; Zhong, Qiu; Auwanit, Wattana; Ayuthaya, Panasda I.N.; Otake, Toru; Mori, Haruyo; Oishi, Isao; Kurosu, Takeshi; Takahashi, Hirokazu; Mukai, Tetsu; Ikuta, Kazuyoshi.

In: Vaccine, Vol. 19, No. 20-22, 06.04.2001, p. 3019-3032.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes

AU - Komoto, Satoshi

AU - Kinomoto, Masanobu

AU - Ibrahim, Madiha S.

AU - Zhong, Qiu

AU - Auwanit, Wattana

AU - Ayuthaya, Panasda I.N.

AU - Otake, Toru

AU - Mori, Haruyo

AU - Oishi, Isao

AU - Kurosu, Takeshi

AU - Takahashi, Hirokazu

AU - Mukai, Tetsu

AU - Ikuta, Kazuyoshi

PY - 2001/4/6

Y1 - 2001/4/6

N2 - The viral accessory gene product Nef has been shown to play an important role in human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis. Only little information is available regarding the differences in the host immune responses against Nef protein and its function in vivo among different subtypes of HIV-1. In the present study, we showed marked differences in the immune responses to Nef protein between subtypes B and E. The amino acid sequence in subtype E Nef showed 72% homology with that in subtype B. Most murine monoclonal antibodies obtained by immunization with subtype B or E Nef protein showed cross-reactivity with both Nef proteins (80 and 67%, respectively). Next, we focused on the immune responses among infected Japanese and Thai individuals. Subtyping of the individuals into B and E was carried out by enzyme-linked immunosorbent assay (ELISA) using synthetic peptides corresponding to the V3 loop representing the principal neutralizing domain. Most of the sera from these individuals reacted strongly with Gag p24 proteins derived from subtypes B and E at similar levels. However, the immune responses among these individuals to Nef protein were markedly different. Some subtype B-infected Japanese and Thai individuals (40 and 35%, respectively) showed higher levels of anti-Nef antibodies, although these antibodies preferentially recognized epitopes specific to subtype B. On the other hand, most of the subtype E-infected Japanese and Thai individuals showed low or no antibody responses to Nef proteins. Thus, immune responses to Nef were markedly different between subtypes B- and E-infected carriers, suggesting different function(s) for Nef in AIDS pathogenesis. Further, vaccine design must take into account the different subtypes of HIV-1.

AB - The viral accessory gene product Nef has been shown to play an important role in human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis. Only little information is available regarding the differences in the host immune responses against Nef protein and its function in vivo among different subtypes of HIV-1. In the present study, we showed marked differences in the immune responses to Nef protein between subtypes B and E. The amino acid sequence in subtype E Nef showed 72% homology with that in subtype B. Most murine monoclonal antibodies obtained by immunization with subtype B or E Nef protein showed cross-reactivity with both Nef proteins (80 and 67%, respectively). Next, we focused on the immune responses among infected Japanese and Thai individuals. Subtyping of the individuals into B and E was carried out by enzyme-linked immunosorbent assay (ELISA) using synthetic peptides corresponding to the V3 loop representing the principal neutralizing domain. Most of the sera from these individuals reacted strongly with Gag p24 proteins derived from subtypes B and E at similar levels. However, the immune responses among these individuals to Nef protein were markedly different. Some subtype B-infected Japanese and Thai individuals (40 and 35%, respectively) showed higher levels of anti-Nef antibodies, although these antibodies preferentially recognized epitopes specific to subtype B. On the other hand, most of the subtype E-infected Japanese and Thai individuals showed low or no antibody responses to Nef proteins. Thus, immune responses to Nef were markedly different between subtypes B- and E-infected carriers, suggesting different function(s) for Nef in AIDS pathogenesis. Further, vaccine design must take into account the different subtypes of HIV-1.

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