AEGiS-15IAC: Pertussis toxin B-oligomer (PTX-B) inhibits HIV replication in human lymphoid histocultures: Evidence for an inducible latent reservoir.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Pertussis toxin B-oligomer (PTX-B) inhibits HIV replication in human lymphoid histocultures: Evidence for an inducible latent reservoir.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrA1234)

Alfano M, Grivel JC, Ghezzi S, Corti D, Poli G, Margolis L
AIDS Immunopathogenesis Unit, DIBIT-Scientific Institute San Raffaele, Milan, Italy

BACKGROUND: Both pertussis toxin (PTX) and its non-toxic subunit (PTX B-oligomer, PTX-B) have shown inhibitory activity against HIV-1 replication in several model of in vitro infection, including mitogen-activated PBMC, monocyte-derived macrophages (MDM), and chronically infected U1 cells stimulated by cytokines. PTX-B inhibits entry of CCR5-dependent (R5) HIV-1 strains and suppresses both R5 and CXCR4-dependent (X4) virus replication at post-entry level(s). Here we investigated whether PTX-B or a genetically modified PTX, PT-9K/129G, which retains all the PTX-B activities and it is used as a vaccine against Bordetella pertussis, exerted anti-HIV effect in lymphoid tissues infected ex vivo that do not require in vitro activation for productive infection.

METHODS: Lymphocytes either spontaneously released from human lymphoid tissue (LT) blocks or obtained after their mincing were analyzed for markers of sub-populations, cell activation and prolferation by flow cytometry. Viral production in the culture supernatants (RT activity), and mitogenicity by means of [3H]-Thymidine incorporation and cell counts. Quantification of HIV DNA and RNA was performed by real-time PCR (TaqMan assay).

RESULTS: PTX-B or PT-9K/129G inhibited both R5 and X4 HIV-1 replication in LT. Maximal inhibition was achieved at concentration up to 100 times lower than those required for inhibition of in vitro-infected PBMC or MDM. PTX-B or PT-9K/129G increased the number of lymphocytes spontaneously released from LT containing latently infected cells. Robust HIV replication was induced by PHA, but not by incubation with mitogenic concentration of PTX-B or PT-9K/129G. Conclusion PTX-B or PT-9K/129G represent novel anti-HIV molecules encompassing both immune-activating capacities and antiviral properties.

Keywords: AEGIS, Pertussis Toxin, Virus Replication, HIV-1, Hominidae, Receptors, CXCR4, Receptors, CCR5, Antiviral Agents, Bordetella pertussis, Humans, Animal, In Vitro, virology

040711
WeOrA1234