Recombinant HIV-1 Rev protein (92BR025)

The binding behavior of ritonavir (RTV), a HIV/AIDS protease inhibitor, with ct-DNA was characterized through multiple testing technologies and theoretical calculation. The findings revealed that the RTV-DNA complex was formed through the noncovalent interaction mainly including conventional hydrogen bonds and carbon hydrogen bonds as well as hydrophobic interactions (pi-alkyl interactions). The stoichiometry and binding constant of the RTV-DNA complex were 1:1 and 1.87 x 10(3) M-1 at 298 K, respectively, indicating that RTV has moderate affinity with ct-DNA. The findings confirmed that RTV binds to the minor groove of DNA. The outcomes of CD experiments showed that the binding with RTV changed the conformation of DNA slightly. However, the conformation of RTV had obvious changes after binding to DNA, meaning that the flexibility of RTV molecule played an important role in stabilizing the RTV-DNA complex. Meanwhile, the results of DFT calculation revealed that the RTV and DNA interaction caused the changes in the frontier molecular orbitals, dipole moment and atomic charge distribution of RTV, altering the chemical properties of RTV when it bound to DNA. Communicated by Ramaswamy H. Sarma

Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B-cell dysfunction due to unspecific B-cell activation. How HIV-1 affects antigen-specific B-cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B-cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T-cell-B-cell immune synapse. This interference reduced B-cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.