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Size and Structure of Viral Genomes

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Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
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Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
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Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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Measurement of In Vitro Integration Activity of HIV-1 Preintegration Complexes
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Multimodal Functionalities of HIV-1 Integrase.

Alan N Engelman1,2, Mamuka Kvaratskhelia3

  • 1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Viruses
|May 28, 2022
PubMed
Summary
This summary is machine-generated.

Human immunodeficiency virus 1 (HIV-1) integrase binds genomic RNA, crucial for proper virion formation. Disrupting this interaction causes defective virus particles and impaired replication.

Keywords:
HIVaberrant integrase multimerizationallosteric integrase inhibitorintegraseintegrase-RNA bindingvirus maturationvirus morphogenesis

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Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Integrase is essential for retroviral DNA integration into host genomes.
  • HIV-1 integrase's role in non-catalytic functions like reverse transcription and virion maturation is poorly understood.
  • Previous studies implicated integrase in HIV-1 replication beyond its catalytic role.

Purpose of the Study:

  • To elucidate the mechanisms of HIV-1 integrase in non-catalytic viral replication steps.
  • To investigate the role of integrase-RNA binding in HIV-1 particle morphogenesis and infectivity.
  • To propose a refined classification of class II integrase mutant viruses based on distinct functional defects.

Main Methods:

  • Analysis of integrase-RNA binding in virions.
  • Characterization of virion morphology and composition using mutational and pharmacological approaches.
  • Phenotypic assessment of viral replication defects in integrase mutant viruses.

Main Results:

  • Disruption of integrase-RNA binding leads to eccentric virion particles with external ribonucleoprotein complexes.
  • Defective integrase-RNA binding results in preferential loss of viral components and impaired reverse transcription.
  • Eccentric particle formation and defective integrase-RNA binding are common features of class II integrase mutants.

Conclusions:

  • Integrase-RNA binding is critical for maintaining the structural integrity of HIV-1 virions.
  • New subclasses (a, b, c) of class II integrase mutants are proposed based on distinct defects in RNA binding and morphogenesis.
  • These findings provide new insights into the multifaceted role of integrase in HIV-1 particle maturation and replication.