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 pdfMachine
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 pdfMachine
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 VIROLOGÍA
(Introducción)

Historia
Louis Pasteur Robert Koch

1880-1890 Pasteur y Koch : Teoría infecciosa de las

enfermedades.
En algunos casos, no se encontraban hongos ni
bacterias (descubiertas años atrás), en los fluídos ó
tejidos de los enfermos.
1884 Chamberland (asociado de Pasteur) : inventó un
filtro para obtener agua bacteriológicamente pura, lo
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 VIROLOGÍA
Historia

1892 : Ivanovsky reprodujo la enfermedad del mosaico

del tabaco con savia filtrada. 1er virus vegetal
reportado.

1898 Beijerink : Reprodujo lo anterior e interpretó que

“la enfermedad no era producida por microbios sino
por un virus líquido viviente”. (antes, virus se usaba
para designar “veneno”. También se les llamó
“Agentes filtrables”)

1898 Loëffler y Frosch : Fiebre aftosa de bovinos. 1er

virus animal reportado.
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 VIROLOGÍA
Historia

1901 : Virus de la fiebre amarilla

1908 : Leucosis linfoide de gallinas Asociación con cáncer
1911 : Sarcoma de Rous

(Viruela bovina : 1798 Primera inmunización artificial,

llamada “vacuna” por la viruela bovina o vacuna.)

1915 y 1917 : Bacteriófagos

1920-1950 : Desarrollo de técnicas de estudio de los
virus: filtros, cultivo en huevos embrionados, ratones,
cultivos celulares (virologia cuantitativa), cristalografía,
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 VIROLOGÍA
Historia

60’s Comportamiento epidemiológico

70’s Viroides(sin cápside y con sólo una cadena de RNA
80’s – 2000 Biología molecular viral
1981 – Priones : Proteínas infecciosas. Vacas locas,
Creutzfelt-Jacob en humanos.

80’s Inmunodeficiencias humanas

Oncogenes

Gran impacto en la humanidad. Registros sXV ac.

Momias : poliomielitis, viruela

Uso de virus como herramientas : Terapia Génica

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 VIROLOGÍA
Qué son los virus : Son paquetes de ácidos
nucléicos rodeados de cubiertas
protectoras

No generan energía metabólica, ni sintetizan proteínas

por sí mismos.

Contienen DNA ó RNA, pero no ambos a la vez.

Su DNA ó RNA puede ser de simple cadena, ó de doble

cadena.

Varían en complejidad : Qß : 3 genes / Poxvirus

(viruela) : 240 genes

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 Complejidad de algunos virus
Acido Nucléico Virus representativos # aprox. de
genes
DNA cadena simple Fago ∮X174 5

DNA cadena doble Virus del Polioma 6

Adenovirus 2 30
Fago T4 150
Viruela 240

RNA cadena simple Fago Qß 3

Sarcoma de Rous 4
Mosaico del tabaco 6
Polio 8
Virus de la gripe 12

RNA doble cadena Reovirus 22

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 Los virus pueden infectar
cualquier forma de vida

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 Los virus se diferencian de los
seres vivos en

Estructura

Biología

Reproducción

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 El material genético está en una
cubierta protéica llamada cápside

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VIROLOGÍA
Tamaños : 20-300 nm

(1nm = 10-9 m)

Bacteria : 2 µm

(1µm = 1000nm)

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 Comparación de tamaños
Item µm Å Veces virus

Atomo de H 0.0001 1 0.001

Proteína Globular 0.004 40 0.04

Virus grande 0.1 1 x 104 1

E. Coli 2 2x105 20
Espermatozoide sin cola 1x5 1x105 X 5x105 10 x 50

Eritrocito 9 9x105 90

Célula somática 10-30 1-3 x 106 100 - 300

Ameba 90 9 x 106 900

Ovulo humano 100 1 x 107 1000

Huevo de sapo 2000 2 x 108 20000

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 Principales familias de virus
Ortomixovirus Arenavirus

Paramixovirus Poxvirus (viruela) Los + complejos

Rhabdovirus Parvovirus

Retrovirus Papovavirus

Coronavirus Adenovirus

Picornavirus Herpesvirus

Reovirus Iridovirus

Togavirus Bacteriófagos

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Características estructurales de los virus
Un sólo ácido nucleico (cca biológica fundamental)

Cubierta ó Cápside (Envoltura protéica) que envuelve

al ácido nucléico.

Los más simples sólo tienen ambos elementos. Se les

llama virus “desnudos”.

Otros más complejos, tienen además una capa lipídica.

Se les llama virus “envueltos”.

Los virus “envueltos” son menos resistentes que los

“desnudos”. Ej. Ataque de solventes orgánicos (ie.Eter)

Formas variadas :
Icosaédricos : (20 caras, 12 ángulos)
Cilíndricos ó helicoidales : Mosaico del tabaco
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Características estructurales de los virus
Un sólo ácido nucleico (característica biológica
fundamental)

Todos los de RNA son simple

cadena excepto : Reovirus y
Birnavirus

Todos los de DNA son doble

cadena excepto : Parvovirus
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Características estructurales de los virus
El material genético de los virus es muy pequeño y
limitado.

La cubierta de los virus está formada por el

ensamblaje de una o pocas subunidades
repetidas muchas veces.
# aas >> # nucleótidos

TMV : 340.000 residuos

6400 nucleótidos

No puede haber tanto DNA para toda la cubierta

protéica.  repetición, repetición, repetición.

TMV : 2130 proteínas idénticas (158 aas)

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 Factores que determinan la forma de
las cápsides
Buckminster Fuller (1895-1983)– Arquitecto, inventor,
ingeniero, escritor, matemático, educador, humanista :
Domos

Tensegridad : Término de Arquitectura

Domos o Cilindros favorecidos energéticamente

Corte 2-D de la nube de densidad electrónica de un
domo viral.

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 Ejemplos de “domos virales”

Buckminster Fuller / Donald Caspar y Aaron Klug

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 pdfMachine
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 Icosaédrico Helicoidal

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 pdfMachine
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 Consideraciones para la
estructura de un virus

•Uso de una o pocas proteínas muy

repetidas

•Organizadas en un número limitado de

formas.

•La estabilidad se da con el máximo # de

enlaces, y usando cada vez el mismo tipo
de contactos.

•La estructura resultante debe ser

simétrica.
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 Estructuras ideales

•Estructura cilíndrica con simetría

helicoidal

•Estructura esférica con simetría

icosaédrica.

•De hecho todos los virus pequeños son

cilindros, esferas, ó una combinación de
ambas.
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 Icosaédrico Helicoidal

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 Doble Triple

Dos tipos de simetría cíclica

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 Doble Cuádruple

Doble

Doble

Doble
Doble

Dos tipos de simetría dihédrica

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 Quíntuple

Triple

Doble

Simetría Icosahédrica
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 Proteína del TMV
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 Ensamblaje del TMV

Cada subunidad se une a

tres nucleótidos del RNA
viral (reconocimiento de la
secuencia)
Fraenkel y Williams,
1955, demostraron
que poniendo RNA La unión no es covalente.
viral y las CH3-CH2-COOH
proteínas, obtenían
virus armados,
Primer ejemplo de
indistinguibles de los
AUTOENSAMBLAJE
obtenidos de hojas
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 El RNA RNA
Subunidad
queda Protéica
protegido
del ataque
de las
Rnasas

RNA solo,
se degrada
en unos
minutos.

Con las
proteínas
puede durar
décadas.
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 Bacteriófago T4

Mucho más complejo que el

TMV (6 genes).
T4 : dsDNA : 165 genes

Cabeza, cola, y 6 fibras de

la cola.

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 Bacteriófago T4
Cabeza, cola, y 6 fibras de la cola.
DNA muy empaquetado en la cápside
(56µm en capside de 0.1µm).

Genes de T4 #
Metabólicos (esenciales) 22
Metabólicos (no esenciales) 60
Ensamblaje (proteínas estructurales) 40
Ensamblaje (Otras proteínas) 13
Número total de genes identificados 135

Genes tempranos inmediatos

Genes tempranosuinmediatos
diferidos
Interrumpen la síntesis de proteínas bacterianas
Tempranos diferidos
Genes tardíos
Dnasa degrada DNA bacteriano
DNA T4 Hidroximetil-Citosina
Enzimas que modifican C, y Glicosilan algunos HMC.

Genes tardíos
Replicación del DNA del fago
Proteínas de la Cápside
Lisozima (digiere pared celular bacteriana)
Proteínas de ensamblaje de virus

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 Bacteriófago T4

3 vías independientes: Cabeza, Cola, Fibras

Orden secuencial. Fin de una vía, acelera la
siguiente (E de enlace baja la E de activación )

Ensamblaje de Cabeza y cola. Luego fibras se

unen a la placa basal

No es solo autoensamblaje : Proteínas de

andamiaje (moldes transitorios) y proteasas
(precursor de proteína de la cabeza)

DNA entra en la cabeza formada

Forma de ovillo de lana. Cabeza se
Expande.

Poco conocida la forma de inyección

del DNA.

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 Entrada de un virus

Parásito intracelular obligado

Receptor, Endocitosis

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 Entrada de un virus

Parásito intracelular obligado

Receptor, Endocitosis

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 Estrategias de Replicación de
Virus RNA
•Las células huésped no tienen las enzimas para
replicar RNA (a partir de RNA).

•Deben tener información para RNA polimerasa

dirigida por RNA (RNA replicasa ó RNA sintetasa),
ó para pasar su RNA a DNA (Transcriptasa
Reversa)

•Se clasifican por la relación de su RNA con el

mRNA

•mRNA = RNA (+) / Su complementaria : RNA (-)

•Se conocen cuatro vías de replicación

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 ∓
RNA(-) RNA( )
Clase 2
Rabia Clase 3
Estomatitis vesicular Reovirus

∓
RNA(-) mRNA(+) DNA( ) DNA(-)

Clase 1 Clase 4 RNA(+)

Polio Retrovirus
Fago Qß
RNA(+)
RNA(+)

Estrategias de Replicación de Virus RNA

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 Evolución darwiniana de Fagos

RNAs y replicasas del Fago Qß con rNTPs,

incubadas 20 min.

Se tomó una alícuota de esto, y se repitió la

incubación con nuevas replicasas y rNTPs.

75 repeticiones, tiempos de replicación cada

vez mas cortos.

12% del RNA original de Qß!!!

Se cortaba lo no esencial
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 Bacteriófago Lambda (ë)
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 Replicación viral
No organelas, no capacidad
metabólica, no ribosomas 
Intracelulares Obligados

Infección específica (no cualquier célula)

Conceptos : susceptibilidad, Ciclos
replicativos.

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 Replicación viral

Fase
de
Eclipse

Descenso
en la
producción
de progenie
viral

Fase de
Maduración
y Liberación

Tiempo

8 horas (poliovirus)
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 Pasos en la Replicación viral
1. Adherencia de los viriones a la célula

2. Penetración (material genético, con ó sin otros

componentes)

3. Decapsidación ó desnudamiento (Expone el material

genético)

4. Expresión de los genes virales

5. Producción de componentes del virión

6. Ensamblaje del virión

7. Liberación del virus infeccioso

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 Pasos en la Replicación viral

1. Adherencia

La unión del virus ocurre por un ligando (una

proteína de la superficie del hospedero

Ejs : Integrina ICAM-1 – Rhinovirus

CD4 – VIH

Estos receptores tienen su propia función. El

virus ha evolucionado para “usar” esos
receptores para su adherencia a la célula.
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 Pasos en la Replicación viral

2. Penetración

Casi inmediata a la adherencia

Uno de los siguientes mecanismos

a. Paso directo del virus a través de la
membrana plasmática de la célula
hospedera
b. Endocitosis de la partícula viral
c. Fusión de la envoltura del virus con la
membrana plasmática
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www.hopkins-aids.edu/hiv_lifecycle/hivcycle_flsh.html
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 Pasos en la Replicación viral

3. Desnudamiento

El genoma y las transcriptasas (cuando

aplique) quedan libres en el citoplasma
celular

En ocasiones sólo una porción de la cápside

es removida. membrana plasmática

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 pdfMachine
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 Estrategias de Replicación viral

Evolución viral, ha producido varios

mecanismos.

a. Organización de los genes

b. Expresión genética
c. Replicación de los genomas
d. Ensamblaje y maduración de nuevas
partículas virales

Antes que nada, el virus debe presentar a la

célula, un mRNA que ella pueda reconocer
como tal y traducirlo.
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 Estrategias de Replicación viral
Restricciones :

1. La célula sintetiza su propio mRNA 

carece de las enzimas para :
a. Sintetizar mRNA a partir de RNA
genómico.
b. Enzimas capaces de transcribir el
RNA viral.

2. Eucariotes sólo reconocen genes con

inicios únicos.

Virus  producir varios mRNAs, ó grandes

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 Estrategias de Replicación viral
Restricciones :

3. Competencia con genes celulares.

Necesitan :
Ventaja competitiva

Inhibibión de síntesis de mRNA celulares.

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 Estrategias de Replicación viral
Ensamblaje y liberación

Herpesvirus : Núcleo

Picornavirus, Reovirus, Adenovirus,

Parvovirus, Poxvirus : Citoplasma

RNAvirus con envoltura : Ortomixovirus,

Paramixovirus, Arenavirus, Rhabdovirus,
Togavirus, Retrovirus, Bunyavirus,
Flavivirus, Torovirus, Coronavirus :
Membranas celulares

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 5000 nucleótidos
50-60 proteínas

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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 pdfMachine
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 HERPES VIRUS

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 pdfMachine
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