Identificación de un nuevo factor soluble anti - VIH
Author
Zaldívar Notario, IreneEntity
UAM. Departamento de Biología MolecularDate
2007-06-21Subjects
Infecciones por VIH - Tratamiento - Tesis doctorales; Sida - Tesis doctorales; Polipéptidos - Tesis doctorales; Proteínas - Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 21-06-2007Abstract
Inhibition of HIV infection by expression of genes that interfere with the replicative
life cycle of HIV is a strategy that unlike current drug-based regimes may result in
eradication of the virus. In this study we investigate the inhibitory effect on HIV
replication of a CD4 chimera that is retained in the endoplasmic reticulum (CD4ε15).
Retroviral vector-mediated expression of CD4ε15 interferes with HIV replication by
preventing the processing of HIV envelope protein precursor gp160, to the mature
glycoproteins gp120 and gp41. This mode of action implies that viral gene expression is
permitted but infective viruses are not produced. Therefore, it could be anticipated that
for gene therapy with CD4ε15 to be effective most HIV target cells must be transduced.
Strinkingly, HIV replication was strongly inhibited (up to 100,000-fold) even when a
minority of the T cell population (10%) was transduced with CD4ε15 chimera. This
result indicated that CD4ε15 expressing cells exerted a bystander protective effect on
non-transduced cells. The bystander effect is demonstrated in transwell experiments to
be mediated by a soluble factor. Furthermore, the soluble antiviral factor is released to
the culture supernatant of CD4ε15-expressing cells when infected with HIV. The fact
that the antiviral factor can be released by non-activated CD4+ T cells, together with its
dependency on HIV infection and CD4ε15 expression, indicate that this factor is
different to interferons, chemokines, CAF, and other previously identified antiviral
factors.
Finally, the results indicate that the antiviral soluble factor is a fragment of gp120
viral protein (that we have called EDAF “Env Derived Antiviral Factor”). The
identification of EDAF has been possible by using a combination of biochemical
techniques and proteomics. The identification of the new antiviral factor could open a
new therapy for HIV treatment.
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