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

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Retrovirus Life Cycles

A retrovirus is a single-stranded RNA virus that binds to specific cell surface receptors on a targeted host cell&#39;s outer membrane, fuses, and enters via endocytosis to replicate its genetic material in a unique way.

After enter the host&#39;s cell, the capsid is uncoated and the enzyme reverse transcriptase or RT binds to the viral RNA, synthesizing complementary DNA and with time, double-stranded DNA the reverse of the usual pattern.

Inside the nucleus of the host cell, the viral DNA is integrated into the host DNA forming a provirus.&nbsp;Thus the viral DNA is actively transcribed whenever the host DNA is transcribed, forming messenger RNA.

This mRNA exits the nucleus, enters the cytoplasm, and is translated to form new viral proteins, which can then assemble into new retroviruses that butt out of the cell and are ready to infect other cells.

retrovirus life cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host&rsquo;s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host&rsquo;s genome is transcribed, allowing the retrovirus to replicate. New retroviral RNA is transported to the cytoplasm, where it is translated into proteins that assemble new retroviruses.

<h4>Antiretroviral Drugs Target Different Stages of the HIV Life Cycle</h4>

Particular drugs have been developed to fight retroviral infections. These drugs target specific aspects of the life cycle. One class of antiretroviral drugs, fusion inhibitors, prevents the entry of the retrovirus into the host cell by inhibiting the fusion of the retrovirus with the host cell membrane. Another class of antiretrovirals, reverse transcriptase inhibitors, inhibits the reverse transcriptase enzymes that make DNA copies of the retroviral RNA genome. Reverse transcriptase inhibitors are competitive inhibitors; during the process of reverse transcription, the drug molecules are incorporated into the growing DNA strand instead of the usual DNA bases. Once incorporated, the drug molecules block further progress by the reverse transcriptase enzyme. The third class of drugs, integrase inhibitors, prevents the integrase enzymes from integrating the retroviral genome into the host genome. Finally, protease inhibitors interfere with the enzymatic reactions that are necessary for producing fully functioning retroviral particles.

Combinations (or &ldquo;cocktails&rdquo;) of antiretrovirals are used to fight Human Immunodeficiency Virus (HIV). If left untreated, this retrovirus causes AIDS. Cocktails of antiretrovirals are necessary to fight HIV infections because the retrovirus can quickly evolve resistance to any one drug. This capacity for rapid evolution stems from the single-stranded RNA genome of HIV, which accumulates mutations more rapidly than DNA or double-stranded genomes. Some of these mutations confer drug-resistance.

However, by combining drugs that target events at the beginning, middle, and end of the retroviral life cycle, antiretroviral cocktails (called highly active antiretroviral therapy, or HAART) dramatically reduce the HIV population in a patient. The likelihood of multiple mutations that confer resistance to various drugs in the HIV genome is much lower than that of a single resistant mutation, making the HAART strategy much more effective than single-drug therapies. This cocktail strategy has been enormously successful in treating HIV, such that it is now uncommon for treated individuals to develop AIDS.

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme ...

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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...

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.

How Retroviruses Replicate in Host Cells | JoVE K12

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How Retroviruses Replicate in Host Cells

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