retrovirus

retrovirus
Name	Retrovirus
Taxon	Retroviridae
Subdivision ranks	Subfamilies and genera
Subdivision	Orthoretrovirinae, Spumaretrovirinae

retrovirus. A retrovirus is an RNA virus that replicates within a host cell through the process of reverse transcription, converting its RNA genome into DNA which is then integrated into the host's genome. This unique replication strategy, dependent on the viral enzyme reverse transcriptase, distinguishes retroviruses from other viral families and is central to their biology and pathogenicity. Notable members include the human pathogens Human immunodeficiency virus and Human T-lymphotropic virus, as well as many viruses studied in model organisms like the Rous sarcoma virus in chickens.

Introduction

The discovery of reverse transcriptase in 1970 by Howard Temin and David Baltimore, for which they shared the Nobel Prize in Physiology or Medicine, fundamentally altered the Central dogma of molecular biology and established the retrovirus family. Early work on avian and murine retroviruses, such as those studied at the Rockefeller University and the National Institutes of Health, provided the foundational models for understanding viral oncogenesis. The subsequent emergence of the AIDS pandemic brought global attention to the HIV/AIDS crisis, making retroviruses a major focus of biomedical research and public health initiatives led by organizations like the World Health Organization and the Centers for Disease Control and Prevention.

Structure and Classification

Retrovirus virions are enveloped particles approximately 100 nm in diameter, containing a diploid, single-stranded RNA genome. The viral envelope, derived from the host cell membrane, is studded with glycoproteins like the gp120 of HIV-1 that mediate entry into target cells. Internally, the capsid core houses the genome complexed with nucleocapsid proteins and essential enzymes including reverse transcriptase and integrase. The family Retroviridae is divided into two subfamilies: Orthoretrovirinae, which includes genera like Alpharetrovirus, Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Epsilonretrovirus, and Lentivirus; and Spumaretrovirinae, containing the foamy viruses. Classification is based on virion morphology, genetic complexity, and disease association, as codified by the International Committee on Taxonomy of Viruses.

Life Cycle

The retroviral life cycle begins with attachment and entry via specific interactions between viral envelope proteins and host cell receptors, such as the binding of HIV-1 to CD4 and co-receptors like CCR5. Following fusion and uncoating, reverse transcription occurs in the cytoplasm, producing a double-stranded DNA copy of the viral RNA genome. This viral DNA, or provirus, is then transported into the nucleus and integrated into the host chromosome by the viral integrase, a step that is a hallmark of persistent infection. Subsequent transcription by host RNA polymerase II produces new viral genomic RNA and mRNA, which are translated into viral proteins. Assembly of new virions occurs at the plasma membrane, followed by budding and maturation, where the viral protease cleaves precursor polyproteins into functional units.

Types of Retroviruses

Retroviruses are categorized into simple and complex types based on their genetic organization. Simple retroviruses, such as Murine leukemia virus and Avian leukosis virus, typically contain only the core genes gag, pol, and env. Complex retroviruses, like all lentiviruses including HIV-2 and Simian immunodeficiency virus, and deltaretroviruses like Human T-lymphotropic virus 1, encode additional regulatory proteins such as Tat and Rev that control gene expression. Endogenous retroviruses, which constitute a significant portion of the human genome, are remnants of ancient germline infections; their study has been advanced by researchers at institutions like the Salk Institute and the Wellcome Sanger Institute.

Replication and Pathogenesis

The integration of the provirus into the host genome underlies the unique pathogenesis of retroviruses. This can lead to insertional mutagenesis, where viral integration disrupts or activates host genes like oncogenes or tumor suppressor genes, a mechanism central to cancers induced by viruses like Human T-lymphotropic virus 1 which causes Adult T-cell leukemia/lymphoma. The error-prone nature of reverse transcriptase contributes to high genetic variability, facilitating immune evasion and drug resistance, particularly in HIV-1 infection. Persistent viral replication can cause direct cytopathic effects, as seen in the depletion of CD4+ T cells during AIDS, or chronic immune activation leading to pathologies observed in patients from regions like the Caribbean and Southwestern Japan.

Clinical Significance and Treatment

Retroviruses are responsible for several major human diseases. HIV-1 and HIV-2 are the causative agents of AIDS, a global pandemic first recognized in the United States in 1981. Human T-lymphotropic virus 1 is associated with HTLV-1-associated myelopathy and adult T-cell leukemia, with endemic areas including Kyushu and Sub-Saharan Africa. Treatment primarily involves antiretroviral therapy targeting key steps in the viral life cycle, such as reverse transcriptase inhibitors like Zidovudine, protease inhibitors, and integrase strand transfer inhibitors like Raltegravir. Research into curative strategies, including gene editing approaches like CRISPR investigated at the University of Pennsylvania, and preventive vaccines, remains a high priority for agencies like the National Institute of Allergy and Infectious Diseases.

Category:Viruses Category:Infectious diseases