What Is a Retrovirus?

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The human immunodeficiency virus (HIV) is a retrovirus whose genes are encoded with ribonucleic acid (RNA) instead of deoxyribonucleic acid (DNA).

A retrovirus differs from a traditional virus in the way that it infects, replicates, and causes disease.

HIV is one of only two human retroviruses of its class, the other of which is human T-lymphotropic virus (HTLV).

Scientist in lab

Thana Prasongsin / Getty Images

What Is a Retrovirus?

HIV and HTLV are classified as Group IV RNA viruses of the family Retroviridae. They work by inserting their genetic material into a cell then changing its genetic structure and function in order to replicate itself.

HIV is further classified as a lentivirus, a type of retrovirus that binds to a specific protein called CD4.

Retroviridae viruses can infect mammals (including humans) and birds and are known for causing immunodeficiency disorders as well as tumors.

Their defining characteristic is an enzyme called a reverse transcriptase, that transcribes RNA into DNA.

Under most circumstances, cells convert DNA into RNA so it can be made into various proteins. But in retroviruses, this process happens in reverse (hence the "retro" part), where the viral RNA is turned into DNA.

How HIV Infects

HIV differs from HTLV in that the latter is a deltaretrovirus. While both are characterized by reverse transcription, lentiviruses aggressively replicate, while deltaretroviruses have minimal active replication once an infection has been established.

In order for HIV to infect other cells in the body, it goes through a seven-step life (or replication) cycle, resulting in turning a host cell into an HIV-generating factory. Here's what happens:

  1. Binding: After finding and attacking a CD4 cell, HIV attaches itself to molecules on the surface of the CD4 cell.
  2. Fusion: Once the cells are bound together, the HIV viral envelope fuses with the CD4 cell membrane, allowing HIV to enter the CD4 cell.
  3. Reverse transcription: After it makes it inside a CD4 cell, HIV releases and then uses a reverse transcriptase enzyme to convert its RNA into DNA.
  4. Integration: The reverse transcription gives the HIV the chance to enter the CD4 cell's nucleus, where, once inside, it releases another enzyme called integrase, which it uses to insert its viral DNA into the DNA of the host cell.
  5. Replication: Now that the HIV is integrated into the host CD4 cell's DNA, it starts using the machinery already inside of the CD4 cell to create long chains of proteins, which are the building blocks for more HIV.
  6. Assembly: Now, the new HIV RNA and HIV proteins manufactured by the host CD4 cell move to the surface of the cell and form immature (noninfectious) HIV. 
  7. Budding: This immature HIV—which isn't able to infect another CD4 cell—then forces its way out of the host CD4 cell. There, it releases another HIV enzyme called protease, which breaks up the long protein chains in the immature virus. In doing so, it creates the mature—and now infectious—virus, which now is ready to infect other CD4 cells.

Targets for Therapy

By understanding the mechanisms of replication described above, scientists are able to target and block certain stages of the HIV life cycle.

By disrupting its ability to replicate, the virus population can be suppressed to undetectable levels, which is the goal of HIV antiretroviral drugs.

Currently, there are nine different classes of antiretroviral drugs used to treat HIV, grouped by the stage of the life cycle they block:

Entry/Attachment Inhibitor

What they do: Bind to a protein on the outer surface of HIV, preventing HIV from entering CD4 cells.

Drug(s) in this class: Fostemsavir

Post-Attachment Inhibitor

What they do: Block CD4 receptors on the surface of certain immune cells that HIV needs to enter the cells.

Drug(s) in this class: Ibalizumab-uiyk

Fusion Inhibitor

What they do: Block HIV from entering the CD4 cells of the immune system.

Drug(s) in this class: Enfuvirtide

CCR5 Antagonists

What they do: Block CCR5 coreceptors on the surface of certain immune cells that HIV needs to enter the cells.

Drug(s) in this class: Maraviroc

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

What they do: Block reverse transcriptase, an enzyme HIV needs to make copies of itself.

Drug(s) in this class: Abacavir, emtricitabine, lamivudine, tenofovir disoproxil fumarate, zidovudine 

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

What they do: Bind to and later alter reverse transcriptase, an enzyme HIV needs to make copies of itself.

Drug(s) in this class: Doravirine, efavirenz, etravirine, nevirapine, rilpivirine   

Protease Inhibitors (PIs)

What they do: Block HIV protease, an enzyme HIV needs to make copies of itself.

Drug(s) in this class: Atazanavir, darunavir, fosamprenavir, ritonavir, saquinavir, tipranavir

Integrase Strand Transfer Inhibitor (INSTIs)

What they do: Block HIV integrase, an enzyme HIV needs to make copies of itself.

Drug(s) in this class: Cabotegravir, dolutegravir, raltegravir

Pharmacokinetic Enhancers ("boosters")

What they do: Used in HIV treatment to increase the effectiveness of an HIV medicine included in an HIV regimen.

Drug(s) in this class: Cobicistat

Why Isn't There One Antiretroviral Drug That Can Do It All?

Because of the high genetic variability in HIV, combination antiretroviral therapy is needed to block different stages of the life cycle and ensure durable suppression. To date, no single antiretroviral drug is able to do this.

Challenges and Goals

Lentiviruses replicate aggressively—with a doubling time of 0.65 days during acute infection—but that process of replication is prone to error. This translates to a high rate of mutation, during which multiple HIV variants can develop in a person within a single day.

Many of these variants are nonviable and unable to survive. Others are viable and pose challenges to treatment and the development of vaccines.

Drug Resistance

One significant challenge to effectively treating HIV is the virus's ability to mutate and reproduce while a person is taking antiretroviral medications.

This is called HIV drug resistance (HIVDR), and it can compromise the effectiveness of the current therapeutic options and goal of reducing HIV incidence, mortality, and morbidity.

Wild-Type HIV

HIV drug resistance can develop as the result of something known as "wild-type" HIV, which is the predominant variant within the untreated viral pool, thanks to the fact that it can survive when other variants can't.

The viral population can only start to shift once a person starts taking antiretroviral drugs.

Because untreated HIV replicates so quickly, and frequently includes mutations, it's possible that a mutation can form that is able to infect host cells and survive—even if the person is taking antiretroviral drugs.

It's also possible that the drug-resistant mutation becomes the dominant variant and proliferates. Additionally, resistance can develop as a result of poor treatment adherence, leading to multiple drug resistance and treatment failure.

Sometimes, when people are newly infected with HIV, they inherit a resistant strain of the virus from the person who infected them—something called transmitted resistance. It's even possible for someone newly infected to inherit deep, multidrug resistance to several classes of HIV medications.

Newer HIV Treatments Offer More Protection Against Mutations

Where some older HIV drugs like Viramune (nevirapine) and Sustiva (efavirenz) can develop HIV resistance with but a single mutation, newer drugs require numerous mutations before failure occurs.

Vaccine Development

One of the most significant obstacles to creating a widely effective HIV vaccine is the genetic diversity and variability of the virus itself. Instead of being able to focus on a single strain of HIV, researchers have to account for the fact that it replicates so quickly.

HIV Replication Cycle

The replication cycle of HIV takes a little more than 24 hours.

And while the replication process is fast, it's not the most accurate—producing many mutated copies each time, which then combine to form new strains as the virus is transmitted between different people.

For example, in HIV-1 (a single strain of HIV), there are 13 distinct subtypes and sub-subtypes that are linked geographically, with 15% to 20% variation within subtypes and variation of up to 35% between subtypes.

Not only is this a challenge in creating a vaccine, but also because some of the mutated strains are resistant to ART, meaning that some people have more aggressive mutations of the virus.

Another challenge in developing a vaccine is something called latent reservoirs, which are established during the earliest stage of HIV infection, and can effectively “hide” the virus from immune detection, as well as the effects of ART.

This means that if the treatment is ever stopped, a latently infected cell can be reactivated, causing the cell to begin to produce HIV again.

While ART can suppress HIV levels, it can't eliminate latent HIV reservoirs—meaning that ART cannot cure HIV infection.

Challenges of Latent HIV Reservoirs

Until scientists are able to “clear” latent HIV reservoirs, it is unlikely that any vaccine or therapeutic approach will fully eradicate the virus.

There is also the challenge of the immune exhaustion that comes with a long-term HIV infection. This is the gradual loss of the immune system’s ability to recognize the virus and launch an appropriate response.

Any type of HIV vaccine, AIDS cure, or other treatment must be created taking immune exhaustion into consideration, finding ways to address and offset the decreasing capabilities of a person's immune system over time.

Advances in HIV Vaccine Research

However, there have been some advances in vaccine research, including an experimental strategy called “kick-and-kill.” It is hoped that the combination of a latency-reversing agent with a vaccine (or other sterilizing agents) can succeed with a curative, experimental strategy known as “kick-and-kill” (a.k.a. “shock-and-kill”).

Essentially, it is a two-step process:

  1. First, drugs called latency-reversing agents are used to reactivate latent HIV hiding in immune cells (the "kick" or "shock" part).
  2. Then, once the immune cells are reactivated, the body's immune system—or anti-HIV drugs—can target and kill the reactivated cells.

Unfortunately, latency-reversing agents alone are not capable of reducing the size of the viral reservoirs.

Additionally, some of the most promising vaccine models to-date involve broadly-neutralizing antibodies (bNAbs)—a rare type of antibody that is able to target the majority of HIV variants.

BNAbs were first discovered in several HIV elite controllers—people who appear to have the ability to suppress viral replication without ART and show no evidence of disease progression. Some of these specialized antibodies, like VRC01, are able to neutralize more than 95% of HIV variants.

Currently, vaccine researchers are attempting to stimulate the production of bNAbs.

A 2019 study involving monkeys shows promise. After receiving a single shot of an HIV vaccine, six out of the 12 monkeys in the trial developed antibodies that significantly delayed infection, and—in two cases—even prevented it.

This approach is still in the early stages of human trials, though in March 2020, it was announced that for the first time, scientists were able to devise a vaccine that induced human cells into generating bNAbs.

This is a notable development, following years of past studies, which, up until this point, have been stymied by the lack of a robust or specific bNAb response.

HIV Vectors in Gene Therapy

Inactivated HIV is now being explored as a potential delivery system to treat other diseases—including:

  • Leukemia
  • Severe combined immunodeficiency (SCID)
  • Metachromatic leukodystrophy

By turning HIV into a noninfective “vector,” scientists believe they can use the virus to deliver genetic coding to the cells that HIV preferentially infect.

A Word From Verywell

By better understanding the way that retroviruses work, scientists have been able to develop new drugs.

But even though there are now treatment options that didn't previously exist, a person's best chance of living a long, healthy life with HIV comes down to being diagnosed as early as possible, via regular testing.

An early diagnosis means earlier access to treatment—not to mention the reduction of HIV-associated illness and increases in life expectancy.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Elizabeth Yuko, PhD
Elizabeth Yuko, PhD, is a bioethicist and journalist, as well as an adjunct professor of ethics at Dublin City University. She has written for publications including The New York Times, The Washington Post, The Atlantic, Rolling Stone, and more.