Recent advances in research on hepadnaviral infection in the woodchuck model

Schulte, I.; Zhang, Ejuan; Zhao, Meng; Pei, Rongjuan; Lu, Mengji; Roggendorf, Michael

doi:10.1007/s12250-008-2941-z

Cited by 1 publication

(2 citation statements)

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“…These molecules are stored inside the lytic granules of cytotoxic cells which are secreted upon stimulation. Acting in synergy, perforins produce pores in the target cells membrane allowing the entry of granzymes, and both induce cell death through cytotoxicity mechanisms [ 50 – 52 ]. One of the markers of this degranulation process consists in the molecules CD107a (LAMP-1), glycoproteins associated with the membrane of lysosomal granules that are exposed on the cell surface after activation of the CTL [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…Acting in synergy, perforins produce pores in the target cells membrane allowing the entry of granzymes, and both induce cell death through cytotoxicity mechanisms [ 50 – 52 ]. One of the markers of this degranulation process consists in the molecules CD107a (LAMP-1), glycoproteins associated with the membrane of lysosomal granules that are exposed on the cell surface after activation of the CTL [ 52 ]. The results raised here showed the activation of CTLs and cytotoxic response in short cultures of splenocytes from immunized mice, upon stimulation with HBZ peptides, observed by the production of granzyme B in effector memory T cells and by the expression of CD107a in T CD8 + cells.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Daian e Silva,

Cox,

Rocha

et al. 2023

Virol J

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Background Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. Methods We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. Results T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42–50 and HBZ157–176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L−Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. Conclusions Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

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Section: Discussionmentioning

confidence: 99%