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The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies.

Abstract：

:The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3 peptides corresponding to field isolates were highly immunogenic but failed to induce neutralizing or gp120-precipitating Abs. On the contrary, V3 peptide corresponding to the laboratory strain HXB2 induced HIV neutralizing, gp120-precipitating immune serum. In conclusion, these data suggest a participation of the V3 domain in the immunoselection of escape virus, and that V3 on early field virus is less accessible to NA than that on laboratory strains.

journal_name

Arch Virol

journal_title

Archives of virology

authors

Arendrup M,Akerblom L,Heegaard PM,Nielsen JO,Hansen JE

doi

10.1007/BF01309956

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

655-70

issue

4

eissn

0304-8608

issn

1432-8798

journal_volume

140

pub_type

杂志文章

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