Retroviruses and Human Immunodeficiency Virus

Retroviruses are RNA viruses that replicate through a DNA intermediate: they use the enzyme reverse transcriptase to copy their RNA genome into DNA, which then integrates into the host chromosome as a provirus. This unusual strategy, discovered in 1970, defines the family and underlies the biology of the human immunodeficiency virus (HIV), the cause of AIDS, as well as the human T-lymphotropic viruses.

Definition

Retroviruses are enveloped single-stranded RNA viruses of the family Retroviridae that replicate by reverse-transcribing their genome into double-stranded DNA, which integrates into the host genome as a provirus; in humans the principal pathogens are HIV-1 and HIV-2 and the human T-lymphotropic viruses.

Scope

The entry introduces the retroviruses, the reverse-transcription and integration steps that distinguish them, and HIV as the principal human retroviral pathogen, including its pathogenesis and natural history. It is a reference overview of viral biology and epidemiology and does not provide clinical management, antiretroviral dosing, or treatment guidance.

Core questions

• How does reverse transcription invert the usual flow of genetic information from RNA to DNA?
• Why does integration of a provirus make retroviral infection lifelong?
• How does HIV deplete CD4 T cells and produce progressive immunodeficiency?

Key concepts

• Reverse transcriptase
• Provirus and genomic integration
• Single-stranded RNA genome (diploid)
• Integrase and protease
• CD4 T-cell tropism
• Latent reservoir
• HIV-1 and HIV-2
• Human T-lymphotropic virus (HTLV)

Key theories

Reverse transcription

Howard Temin and David Baltimore independently discovered that RNA tumour viruses carry an RNA-dependent DNA polymerase, showing that genetic information can flow from RNA to DNA and defining the replication strategy of retroviruses.

Mechanisms

After entry, a retrovirus uses its reverse transcriptase to synthesise double-stranded DNA from its RNA genome; viral integrase then inserts this DNA into a host chromosome, where it persists as a provirus and is transcribed using cellular machinery. HIV targets cells bearing the CD4 receptor and a co-receptor, principally CD4 helper T lymphocytes, and progressive loss of these cells produces the immunodeficiency that defines AIDS. Integration into long-lived cells establishes a latent reservoir that current therapies suppress but do not eradicate, and the error-prone reverse transcriptase drives the genetic variability that complicates immune control.

Clinical relevance

HIV infection, if untreated, progresses to profound immunodeficiency and opportunistic disease, and the biology of reverse transcription and integration explains both why retroviral infection is lifelong and why effective drugs target the distinctive viral enzymes. Understanding the latent reservoir clarifies why treatment suppresses but does not cure infection. This entry describes mechanisms and natural history and is not a basis for individual diagnosis or treatment.

Epidemiology

HIV remains a major global pandemic affecting tens of millions of people, transmitted sexually, through blood, and from mother to child; the human T-lymphotropic viruses are endemic in particular regions and associated with specific leukaemia and neurological syndromes.

Evidence & guidelines

The discovery of reverse transcriptase and the isolation of the AIDS-associated retrovirus established the foundations of the field, and authoritative reviews summarise HIV pathogenesis, natural history, and the principles of prevention and treatment (described at the level of evidence, not individual advice).

History

The 1970 discovery of reverse transcriptase by Temin and Baltimore overturned the assumption that genetic information flowed only from DNA to RNA and defined the retroviruses. Following the recognition of AIDS in the early 1980s, Barré-Sinoussi, Montagnier, and colleagues isolated the causative retrovirus in 1983, and subsequent decades transformed a uniformly fatal infection into a manageable chronic condition through antiretroviral therapy targeting the virus's distinctive enzymes.

Key figures

• Howard Temin
• David Baltimore
• Françoise Barré-Sinoussi
• Luc Montagnier
• Robert Gallo

Seminal works

• baltimore-1970
• temin-1970
• barresinoussi-1983
• maartens-2014

Frequently asked questions

What is reverse transcription, and why is it significant?

It is the synthesis of DNA from an RNA template by the enzyme reverse transcriptase. Its discovery showed that genetic information can flow from RNA to DNA, defining how retroviruses replicate and integrate into host DNA.

Why can HIV infection be controlled but not yet cured?

Once the virus integrates into long-lived host cells it forms a latent reservoir; antiretroviral therapy suppresses active replication but does not eliminate this integrated, dormant viral DNA.