Name: how retroviruses replicate in host cells
Uploaded: 2019-03-11T09:21:24.000Z
Duration: 1 min 10 s
Channel: JoVE

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from-molecules-to-organisms-structures-and-processes

From Molecules To Organisms: Structures And Processes

HS-LS1-8

Retrovirus Life Cycles

- [Narrador] Un retrovirus es
un virus de ARN de una hebra

que se une a receptores específicos
de la superficie celular

en la membrana externa de
una célula huésped objetivo,

se fusiona y entra por endocitosis

para replicar su material
genético de una manera única.

Tras de entrar en la célula huésped,

la cápside no está recubierta

y la enzima transcriptasa inversa o RT

se une al ARN viral,
sintetizando ADN complementario

y con el tiempo, se une
a un ADN de doble cadena,

lo contrario del patrón habitual.

Dentro del núcleo de la
célula huésped, el ADN viral

se integra en el ADN del
huésped formando un provirus.

Así el ADN viral se transcribe activamente

cada vez que el ADN huésped se transcribe,

se forma un ARN mensajero.

Este ARNm sale del núcleo,
entra en el citoplasma,

y se traduce para formar
nuevas proteínas virales,

que se ensamblan en nuevos retrovirus

que sales de la célula listos

para infectar otras células.

Greenwood, Alex D., Yasuko Ishida, Sean P. O'Brien, Alfred L. Roca y Maribeth V. Eiden. "Transmisión, evolución y endogenización: lecciones aprendidas de las recientes invasiones retrovirales". Microbiol. Mol. Biol. Rev. 82, no. 1 (1 de marzo de 2018): e00044-17. [<a href="https://doi.org/10.1128/MMBR.00044-17" target="__blank">Fuente</a>]

Atta, Mohamed G., Sophie de Seigneux y Gregory M. Lucas. "Farmacología clínica en la terapia del VIH". Revista clínica de la Sociedad Americana de Nefrología 14, n.º 3 (7 de marzo de 2019): 435–44. [<a href="https://doi.org/10.2215/CJN.02240218" target="__blank">Fuente</a>]

ciclos de vida de los retrovirus

Los retrovirus tienen un genoma de ARN monocatenario que sufre una forma especial de replicación. Una vez que el retrovirus ha ingresado a la célula huésped, una enzima llamada transcriptasa inversa sintetiza ADN bicatenario a partir del genoma de ARN retroviral. Esta copia de ADN del genoma luego se integra en el genoma del huésped dentro del núcleo mediante una enzima llamada integrasa. En consecuencia, el genoma retroviral se transcribe en ARN cada vez que se transcribe el genoma del huésped, lo que permite que el retrovirus se replique. El nuevo ARN retroviral se transporta al citoplasma, donde se traduce en proteínas que ensamblan nuevos retrovirus. <h4>Los medicamentos antirretrovirales se dirigen a diferentes etapas del ciclo de vida del VIH</h4> Se han desarrollado medicamentos particulares para combatir las infecciones retrovirales. Estos medicamentos se dirigen a aspectos específicos del ciclo de vida. Una clase de fármacos antirretrovirales, los inhibidores de la fusión, previenen la entrada del retrovirus a la célula huésped al inhibir la fusión del retrovirus con la membrana de la célula huésped. Otra clase de antirretrovirales, los inhibidores de la transcriptasa inversa, inhiben las enzimas transcriptasa inversa que producen copias de ADN del genoma de ARN retroviral. Los inhibidores de la transcriptasa inversa son inhibidores competitivos. Durante el proceso de transcripción inversa, las moléculas del fármaco se incorporan a la cadena de ADN en crecimiento en lugar de las bases de ADN habituales. Una vez incorporadas, las moléculas del fármaco bloquean el avance de la enzima transcriptasa inversa. La tercera clase de fármacos, los inhibidores de la integrasa, impiden que las enzimas integrasas integren el genoma retroviral en el genoma del huésped. Finalmente, los inhibidores de proteasa interfieren con las reacciones enzimáticas necesarias para producir partículas retrovirales en pleno funcionamiento. Se utilizan combinaciones (o “cócteles”) de antirretrovirales para combatir el Virus de Inmunodeficiencia Humana (VIH). Si no se trata, este retrovirus causa el SIDA. Se necesitan cócteles de antirretrovirales para combatir las infecciones por VIH porque el retrovirus puede desarrollar rápidamente resistencia a cualquier medicamento. Esta capacidad de evolución rápida proviene del genoma de ARN monocatenario del VIH, que acumula mutaciones más rápidamente que el ADN o los genomas de doble cadena. Algunas de estas mutaciones confieren resistencia a los medicamentos. Sin embargo, al combinar medicamentos que se dirigen a eventos al principio, a la mitad y al final del ciclo de vida retroviral, los cócteles antirretrovirales (llamados terapia antirretroviral de gran actividad o TARGA) reducen drásticamente la población de VIH en un paciente. La probabilidad de que se produzcan múltiples mutaciones que confieren resistencia a diversos fármacos en el genoma del VIH es mucho menor que la de una única mutación resistente, lo que hace que la estrategia HAART sea mucho más eficaz que las terapias con un solo fármaco. Esta estrategia de cóctel ha tenido un enorme éxito en el tratamiento del VIH, de modo que ahora es poco común que las personas tratadas desarrollen SIDA.

Ciclos de vida de los retrovirus

Los retrovirus tienen un genoma de ARN monocatenario que se somete a una forma especial de replicación. Una vez que el retrovirus ha entrado en la célula huésped, una enzima ...

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how retroviruses replicate in host cells

Retroviruses replicate by copying their RNA genome into DNA inside a host cell. After entry, the viral enzyme reverse transcriptase makes a double-stranded DNA copy from the single-stranded RNA genome. The viral DNA is then carried into the nucleus and inserted into the host genome by integrase.

Once integrated, the retroviral DNA is transcribed whenever the host genome is transcribed. This produces new viral RNA that can be copied and used again. The new RNA moves into the cytoplasm, where it is translated into proteins that assemble new retroviruses.

Antiretroviral drugs target different steps in the HIV life cycle. Fusion inhibitors block the virus from entering the host cell by stopping fusion with the cell membrane. Reverse transcriptase inhibitors block the enzyme that makes DNA from viral RNA, and they act as competitive inhibitors by being built into the growing DNA strand instead of normal DNA bases.

Other drugs work later in the cycle. Integrase inhibitors prevent viral DNA from joining the host genome, and protease inhibitors interfere with reactions needed to make fully functioning viral particles. Combinations of these drugs, called cocktails, are used against HIV because the virus can quickly evolve resistance to one drug.

HIV has a single-stranded RNA genome, so it accumulates mutations faster than DNA or double-stranded genomes. Some of these mutations can cause drug resistance. Using drugs that act at the beginning, middle, and end of the retroviral life cycle lowers the chance that one virus will resist them all. This highly active antiretroviral therapy, or HAART, has been very successful, and treated individuals now rarely develop AIDS.

How Retroviruses Replicate in Host Cells

what are viruses?

How Viruses Infect Cells and Multiply

Viruses infect cells and make new copies by using a host cell’s own machinery. A virus is a tiny infectious particle with an RNA or DNA genome inside a protective protein coat. It cannot reproduce on its own, so it must enter a cell to make more viruses. After infection, the virus sheds its protein coat and uses the host cell to transcribe and translate its genetic material. The cell then assembles many new viral particles. In many cases, these new viruses rupture the host cell and kill it.

viral structure

How Virus Shapes Help Infection

Viruses have specific structures that help them infect host cells and trigger immune responses. Each virus has a core that contains either a DNA-based or RNA-based genome. That core is surrounded by a protective protein coat called the capsid. The capsid is made of smaller subunits called capsomeres. The capsid and the genome-containing core together are called the nucleocapsid. Viruses are often grouped by capsid design. Most viruses have either icosahedral or helical capsids, but some have...

lytic cycle of bacteriophages

How Phages Infect and Burst Bacteria

Bacteriophages, or phages, are viruses that infect bacteria. They have a distinctive head-tail shape. In the lytic cycle, a phage first attaches to the outside of a bacterial cell. Tail proteins bind to specific receptor proteins on the bacterium’s surface. After attachment, the phage tail injects its DNA genome into the bacterial cytoplasm. The phage then uses the bacterium’s cellular machinery to make proteins needed for replication and dispersal. When phage replication is complete, some of...

lysogenic cycle of bacteriophages

Prophage Integration in Bacteria

The lysogenic cycle shows how bacteriophages can infect bacteria without killing the host right away. In this cycle, the phage genome joins the bacterial genome. The integrated phage DNA is called a prophage, and the bacterium copies it each time it replicates. Some prophages can switch back into the lytic cycle. This change can happen after DNA damage or even without an obvious outside trigger. When the prophage is induced, the phage begins making new virus particles again. Prophages can...

retrovirus life cycles

Retroviruses replicate by copying their RNA genome into DNA inside a host cell. After entry, the viral enzyme reverse transcriptase makes a double-stranded DNA copy from the single-stranded RNA genome. The viral DNA is then carried into the nucleus and inserted into the host genome by integrase. Once integrated, the retroviral DNA is transcribed whenever the host genome is transcribed. This produces new viral RNA that can be copied and used again. The new RNA moves into the cytoplasm, where it...

viral recombination

How Viruses Swap Genes and Spread

Viral gene swapping can happen when more than one virus infects the same cell. After the viruses break open and expose their genomes for replication, matching regions can pair up and exchange sequences. This process is called recombination. Viruses with segmented genomes can also swap whole segments, which is called reassortment. These changes can help create new diseases. Some diseases can infect more than one species. Pigs can be infected by some human and bird viruses, along with the...

viral mutations

How Virus Mutations Drive Outbreaks

Virus mutations can change how quickly a virus evolves and spreads. A mutation is a change in the sequence of bases in DNA or RNA. Some mutations happen when the genome is copied. They are caused by errors made by polymerase enzymes, which replicate DNA or RNA. RNA viruses often change faster than DNA viruses because RNA polymerase does not proofread its work. That means RNA-based genomes, such as HIV, can gather mutations more quickly. Mutation and recombination give viruses the raw material...

key terms and concepts

Learn how retroviruses copy RNA into DNA, integrate into host cells, and how antiretroviral drugs block HIV at key stages of its life cycle.

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How Retroviruses Replicate in Host Cells

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