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.