Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIV(mac251) infection of rhesus macaques; a pilot study

BACKGROUND: HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIV(mac251) macaque model to address whether the route of viral entry influences the kinetics of the appearance and the size of virus-specific immune in different tissue compartments. METHODS: For this purpose, of 2 genetically defined Mamu-A*01-positive macaques, 1 was exposed intravenously and the other intrarectally to the same SIV(mac251) viral stock and virus-specific CD8+ T-cells were measured within the first 12 days of infection in the blood and at day 12 in several tissues following euthanasia. RESULTS: Virus-specific CD8+ T-cell responses to Gag, Env, and particularly Tat appeared earlier in the blood of the animal exposed by the mucosal route than in the animal exposed intravenously. The magnitude of these virus-specific responses was consistently higher in the systemic tissues and GALT of the macaque exposed by the intravenous route, suggesting a higher viral burden in the tissues as reflected by the faster appearance of virus in plasma. Differences in the ability of the virus-specific CD8+ T-cells to respond in vitro to specific peptide stimulation were also observed and the greatest proliferative ability was found in the GALT of the animal infected by the intrarectal route. CONCLUSIONS: These data may suggest that the natural mucosal barrier may delay viral spreading. The consequences of this observation, if confirmed in studies with a larger number of animals, may have implications in vaccine development

Inhibition of tunneling nanotube (TNT) formation and Human T-cell leukemia virus type 1 (HTLV-1) transmission by cytarabine

The human T-cell leukemia virus type 1 (HTLV-1) is highly dependent on cell-to-cell interaction for transmission and productive infection. Cell-to-cell interactions through the virological synapse, bioflm-like structures and cellular conduits have been reported, but the relative contribution of each mechanism on HTLV-1 transmission still remains vastly unknown. The HTLV-1 protein p8 has been found to increase viral transmission and cellular conduits. Here we show that HTLV-1 expressing cells are interconnected by tunneling nanotubes (TNTs) defned as thin structures containing F-actin and lack of tubulin connecting two cells. TNTs connected HTLV-1 expressing cells and uninfected T-cells and monocytes and the viral proteins Tax and Gag localized to these TNTs. The HTLV-1 expressing protein p8 was found to induce TNT formation. Treatment of MT-2 cells with the nucleoside analog cytarabine (cytosine arabinoside, AraC) reduced number of TNTs and furthermore reduced TNT formation induced by the p8 protein. Intercellular transmission of HTLV-1 through TNTs provides a means of escape from recognition by the immune system. Cytarabine could represent a novel anti-HTLV-1 drug interfering with viral transmission

Palmitoylation and p8-mediated human T-cell leukemia virus type 1 transmission.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-13T17:49:03Z No. of bitstreams: 1 Edwards D Palmitoylation and....pdf: 615667 bytes, checksum: e33650b226234c9ea537b06c8947402f (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2014-11-13T17:49:12Z (GMT) No. of bitstreams: 1 Edwards D Palmitoylation and....pdf: 615667 bytes, checksum: e33650b226234c9ea537b06c8947402f (MD5)Made available in DSpace on 2014-11-13T18:05:46Z (GMT). No. of bitstreams: 1 Edwards D Palmitoylation and....pdf: 615667 bytes, checksum: e33650b226234c9ea537b06c8947402f (MD5) Previous issue date: 2013National Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Bahia School of Medicine and Public Health. Bahia Foundation for Science Development. Salvador, BA, BrasilNational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USANational Institutes of Health. National Cancer Institute. Animal Models and Retroviral Vaccines Section. Center for Cancer Research. Bethesda, MD, USAThe orf-I gene of human T-cell leukemia type 1 (HTLV-1) encodes p8 and p12 and has a conserved cysteine at position 39. p8 and p12 form disulfide-linked dimers, and only the monomeric forms of p8 and p12 are palmitoylated. Mutation of cysteine 39 to alanine (C39A) abrogated dimerization and palmitoylation of both proteins. However, the ability of p8 to localize to the cell surface and to increase cell adhesion and viral transmission was not affected by the C39A mutation