A molecular and serologic study of the envelope gene of the British isolate: HIV-1 GB8

The entire envelope gene of a British HIV-1 isolate, GB8, was cloned, sequenced and aligned with those of the reference strains MN, SF2 and IIIB LAI . Three of the viruses (MN, IIIB LAI , GB8) and their recombinant gp120s, were then characterised using an extensive panel of human HIV-1 positive sera and mapped neutralising monoclonal antibodies (MAbs). Overall, the GB8 env-gene translation product shares 84% homology with those of the reference strains. Across the V3 region homology was greater between GB8 and SF2 MN (74.3–88.6%) than IIIB LAI (63.9–66.7%). Accordingly, GB8 was sensitive to V3-specific MAbs which neutralise MN SF2 and resistant to those that neutralize IIIB LAI . In the CD4 binding region the central MWQEVGKAMYAPPI was conserved in all viruses but homology in the N-terminus was greater between GB8 and SF2 and IIIB LAI than MN. GB8 and IIIB LAI were sensitive to all MAbs raised against the CD4 binding site whereas MN was resistant to 3 of 4 tested. Human sera obtained from a London-based cohort did not differentiate between GB8 and MN in neutralisation assays, whereas IIIB LAI titres were significantly lower at all stages of disease. These results show that GB8 carries a consensus-like V3 loop and is as representative as MN of HIV-1 viruses circulating in the UK. To our knowledge, GB8 is the only British HIV-1 isolate which has been characterised to date.