Mutation in the V3 loop of HIV-1 gp120 could affect syncytium formation, virus infectivity and neutralization. To acquire more information of the V3 loop mutation, we analyzed amino acid sequences of the V3 loop of 24 504 isolates from most HIV-1 clades (including A, B, C, D, E, F, G and H clades). The consensus sequence of the V3 loop of each subtype with the highest frequency emerging on each position is constituted and the conservation of each amino acid in this region is also calculated. Exploring the restricted mutation of the V3 region could help to understand mechanism of HIV entry and to develop new strategy against HIV-1.

An effective vaccine is urgently needed to stop AIDS-epidemic. Up to now none of the candidate HIV-vaccines has been developed to prevent HIV-1 infection. A few neutralizing antibodies against HIV-1 enveloping proteins proved to be highly effective to neutralize different strains in vitro. Unfortunately, these antibodies are rare in infected humans, and have never yet been raised by a vaccine. The multiple sequential and antigenic variability of HIV-1 led to unprecedented difficulties in development of effective vaccines and anti-viral drugs. More and more experimental evidences indicated that HIV-1 mutants resulted in immune evasion may be a grave challenge for conventional strategy to prepare effective vaccines. We suggested that epitope-vaccine could be a new strategy to induce high levels of neutralizing antibodies with predefined epitope-specificity against HIV-1. Several candidate epitope-vaccines including mono-epitope-vaccine, multi-epitope-vaccine, epitope-vaccines in combination, were prepared and systematically studied in animal experiments. These studies provided experimental evidences that epitope-vaccine could be a new strategy to develop effective vaccines for prevention and immunotherapy against viral infection of HIV-l or other viruses.

Recent studies demonstrated that the N- and C-domains of HIV-1 gp41 is involved in virus-mediated membrane fusion resulting in HIV-entry into the target cells. Up to now, viral mutation baffled many scientists to develop effective vaccines and drugs against HIV-1. To acquire more information of mutation of gp41 and to reveal the relationship of structure and function of the N- and C-domains, we compared and analyzed amino acid sequences of the gp41 ectodomain (aa 512-681) of 862 isolates from most HIV-1 clades (including A, B, C, D, E, F, G, H, I, J and O clades). A consensus sequence of the ectodomain with the highest frequency emerging on each position is constituted. The fusion domain and the N-domain belong to the most conserved regions in gp41, and most variable residues assemble partial to the C terminal of gp41. The hydrophobicity of each position is also calculated. The a and d positions in the N-domain for maintaining stabilization of the trimeric coiled coil interactions are highly conservative, and the e and g positions in the C-domain to retain the interaction show also highly conservative. The strange high conservation of the c residues may have an implication in the coiled coil structure. The highly conserved residues form the lining of the hydrophobic cavity and the deep cavity is an ideal target for small molecular inhibitors. On the C-terminal of the C-domain there is a highly conserved segment GIVQQQ. They are intimately involved in forming the three interfaces between neighboring helices. The function of the N- and C-domains, such as binding to the potential cellular receptor and inducing protective activities, are also discussed. These studies on the mutation, structure and functions of the N-and C-domains suggested that both domains become a new focus to develop effective vaccine and antiviral drugs in the new strategies.