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Tamiflu (Oseltamivir
phosphate). Inhibe la
neuraminidasa del virus
influenza.
ANTIVIRALES
Los inhibidores no nucleósidos de la transcriptasa reversa (INNTR)
Efavirenz
Delavirdine
Nevirapine
AG AG…… X
Pc
Pv
Tkv
AG AG AG-P
Tkc Pc
http://www.youtube.com/watch?v=9KTDz-ZisZ0
FIG. 3. Viral subversion of cellular apoptotic pathways
DNA RECOMBINANTE:
- GENES CLONADOS Y EXPRESADOS - HEPATITIS B
- DNA DESNUDO - EXPERIMENTAL
PRINCIPLES OF VIROLOGY, 2009
From: Principles of Virology. S.J.Flint, L.W.
Enquist, V.R.Racaneillo, A.M. Skalka. ASM PRESS.
Washington, DC.
PRINCIPLES OF VIROLOGY, 2009
PROBLEMAS DE SEGURIDAD CON LAS VACUNAS A
VIRUS MUERTOS
• HIPERSENSIBILIDAD A • SARAMPION
ANTIGENOS VIRALES
• HIPERSENSIBILIDAD A
ANTIGENOS DE HUEVOS • SARAMPION, PAPERAS
IMMUNOLOGY, ROITT
INTERFERENCIA VIRAL E
INTERFERON
INTERFERENCIA VIRAL E INTERFERON
TIPOS DE INTERFERENCIA:
EJEMPLO:
VIRUS DE LA LEUCOSIS AVIAR, ANULA O INTERNALIZA
LOS RECEPTORES CELULARES PARA EL ROUS
SARCOMA VIRUS.
INTERFERENCIA POR PARTICULAS
DEFECTUOSAS
V-INFLUENZA
ACTIVO
EXP. 2 + = HAY PRODUCCION DE VIRUS
CELULAS M-C
MEDIO EXP. 1 +
CELULAS M-C
EXP. 3 + = NO HAY PRODUCCION DE VIRUS
V-INFLUENZA
ACTIVO
PROPIEDADES DE INTERFERON
2. De 1966 - 1975.
- Se desarrollaron las técnicas para purificar IFN
- Se descubrió PKR y 2’-5’-oligo Adenilato sintetasa.
- Se encontró que IFN inhibía la multiplicación celular
y regulaba la actividad celular.
- Se iniciaron estudios clínicos: actividad antiviral y antitumoral.
3. De 1975 - a la fecha.
- Clonamiento y produccion de IFN recombinante (1979).
- Consolidación de los estudios clínicos y moleculares de IFN.
CARACTERISTICAS DE LOS INTERFERONES HUMANOS
?????
2
mRNA IFN
RIBOSOMAS
3
IFN IFN
IFN
4
IFN
1. VIRUS INFECTA LA CELULA
2. INDUCCION DE LA SINTESIS DEL mRNA PARA INTERFERON (IFN)
3. SINTESIS DE INTERFERON
4. INTERFERON SALE DE LA CELULA
Figure 1.- DNA Sensing and Innate Immunity
TBK-1 = TANK- binding kinase 1 IRFs= Interferon regulatory factors
DAI= DNA-dependent activator of IFN-regulatory factors
Figure 1.- DNA Sensing and Innate Immunity
Shown are signaling pathways that detect microbial DNA in the host cell cytosol
resulting in an innate immune response. In a newly discovered pathway, a cytosolic
DNA-dependent RNA polymerase III (Pol III) detects AT-rich double-stranded DNA
(dsDNA) released by pathogens. Pol III converts this pathogen dsDNA into dsRNA
that has a 5 triphosphate. This RNA species is then sensed by the RNA sensor
RIG-I (Retinoic acid-induced gene I), leading to IFN-β production and activation of
innate immunity. Other well-established pathways sense microbial DNA in different
cellular compartments, triggering production of different sets of cytokines. For
example, Toll-like receptor 9 (TLR9) in endosomes senses CpG motifs in microbial
DNA and activates signaling pathways, culminating in activation of NF- kB and IRF7
with subsequent production of proinflammatory cytokines and type I IFNs. Cytosolic
DNA derived from vaccinia virus can be sensed by AIM2 (Absent in melanoma-2) in
a complex with Asc (apoptosis-associated speck-like protein containing CARD) and
caspase-1, leading to the processing of pro-IL-1β to IL-1β. In certain cultured cell
lines, AT-rich dsDNA can also be sensed by the protein DAI (DNA-dependent
activator of IFN-regulatory factors ), which drives IFN-β production through activation
of the protein kinase TBK-1. Finally, an as yet unknown receptor detects several
types of microbial DNA, including plasmid-derived and GC-rich DNA in some cell
types, leading to IFN-β production via activation of TBK-1.
IRE
[Elemento Regulador de IFN ]
ISG 15
ISG 54, ISG56 and
2,5-OligoA sintetasa , and
Proteina Mx and
PKR (PROTEINA KINASA) and
MHC Clase I , and
MHC Clase II
Antígeno Para Diferenciación de
Células Endoteliales
Maduración de Células B Para
Secreción de Inmunoglobulinas
Proteína de Membrana 20K and
..
PKR eIF2
FT
FT
PKR eIF2-P
FT
eIF2
PKR eIF2
FT eIF2
FT
PKR eIF2-P eIF2
FT
ACTIVA
DEGRADA
2’-5’ PAS
NUCLEASA (RNase L)
.
ACTIVA
FD
n
2’-5-(A)
2’-5’ PASa FD .
ATP
ACTIVA
DEGRADA
2’-5’ PAS
NUCLEASA (RNase L)
A+A+A
ACTIVA
FD
n
2’-5-(A)
ATP
eIF2
PKR eIF2
FT eIF2
FT
PKR eIF2-P eIF2
FT
DEGRADA
2’-5’ PAS
NUCLEASA (RNase L)
A+A+A
ACTIVA
FD
n
2’-5-(A)
ATP
http://www.youtube.com/watch?v=yLDpTM0eSgM
Reverse-Transcriptase Inhibitors HIV: NNRTIs
http://www.youtube.com/watch?v=h7V1eVwxV_c&feature=relmfu