Characterization of a chemokine receptor CCR5-negative T cell line and its use in determining human immunodeficiency virus type 1 phenotype.

A human CD4-positive T cell line from a donor homozygous negative for the chemokine receptor CCR5 was established, characterized, and used for determining the coreceptor usage of human immunodeficiency virus type 1 (HIV-1) isolates. Clones of this IL-2 dependent human T-cell lymphotropic virus type 1 (HTLV-I) immortalized cell line, named IsnoR5 clones 1 and 2, are susceptible to infection by HIV-1 isolates that use CXCR4 as a coreceptor but resistant to infection by CCR5 tropic HIV-1 viruses. HIV-1 isolates whose replication is inhibited in IsnoR5 cells in the presence of the bicyclam AMD 3100, a CXCR4 specific inhibitor, utilize a coreceptor distinct from CCR5 and CXCR4.

Vaccine development using the simian immunodeficiency virus model for AIDS.

Objective: A number of trials in primates using a wide range of putative vaccines based on simian immunodeficiency virus (SIV) have been performed and are summarised here.

Methods: Rhesus macaques and African green monkey (AGMs) were immunised with the test vaccines and challenged with live virus to test the efficacy of the induced or transferred immune responses to protect from infection or disease development.

Results: In initial studies, successful protection from challenge by whole inactivated virus vaccines was subsequently shown to be mediated by immune responses to human cell rather than viral proteins.

Simian immunodeficiency viruses with defective nef genes show increased susceptibility to the noncytotoxic antiviral activity of CD8+ lymphocytes.

The noncytotoxic soluble factor produced by CD8+ T cells inhibits replication of HIV and SIV in vitro and is thought to play a crucial role in combatting infection in vivo. We determined the effect of human CD8+ lymphocytes on the in vitro replication potential of both wild-type and nef-defective mutants of the simian immunodeficiency virus SIVmac251. Although replication of wild-type SIVmac251 in unstimulated human PBMC supplemented with IL-2 was unaffected by the presence of CD8+ T cells, the nef mutants were susceptible to the inhibitory effects.

Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm.

Objective: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2.

Design And Methods: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa.

Protection from pathogenic SIVmac challenge following short-term infection with a nef-deficient attenuated virus.

Infection of rhesus macaques with attenuated SIVmac is, at present, the only strategy which confers significant protection from challenge with wild-type SIVmac grown in monkey PBMC. However, initial results suggest that the protective mechanism does not develop until late after "vaccination" (approx 10 months). As part of a European study using the C8 variant of SIVmac251-32H (containing an in-frame 12-bp deletion in the nef gene), we wished to determine (a) if protection could be achieved against challenge with a "swarm" of SIVmac251-32H produced in monkey cells and (b) if protection could be demonstrated after a short period of infection with the attenuated virus.