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Related Concept Videos

Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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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’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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Viruses with RNA Genomes01:29

Viruses with RNA Genomes

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RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
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Viral Recombination00:57

Viral Recombination

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Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
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Retroviruses02:33

Retroviruses

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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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Size and Structure of Viral Genomes01:26

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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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses
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Pairwise Growth Competition Assay for Determining the Replication Fitness of Human Immunodeficiency Viruses

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Conditionally replicating HIV and SIV variants.

Atze T Das1, Ben Berkhout1

  • 1Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Virus Research
|May 19, 2015
PubMed
Summary
This summary is machine-generated.

Researchers developed controllable human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) variants using doxycycline. These Tet-On engineered viruses offer safer vaccine development and advanced research into viral replication and immune responses.

Keywords:
AIDS vaccineConditional replicationHIVLive-attenuated virusSIVTet-On system

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Area of Science:

  • Virology
  • Immunology
  • Biotechnology

Background:

  • Conditionally replicating human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) are valuable research tools.
  • Existing viral systems lack precise control over replication, posing safety and experimental challenges.

Purpose of the Study:

  • To engineer HIV and SIV variants with a controllable replication mechanism using doxycycline (dox).
  • To assess the utility of these variants in vaccine development and studying immune responses.
  • To investigate the role of viral elements in replication using these engineered viruses.

Main Methods:

  • Replaced natural transcription control with the doxycycline-inducible Tet-On gene expression system in HIV and SIV.
  • Developed HIV-rtTA and SIV-rtTA variants dependent on dox administration for replication.
  • Tested viral replication in various cell/tissue culture systems, human immune system (HIS) mice, and macaques.

Main Results:

  • HIV-rtTA and SIV-rtTA variants are replication-competent but require dox for replication.
  • These variants demonstrate efficient replication and tight dox-dependent control.
  • The engineered viruses successfully replicated in relevant animal models (HIS mice and macaques).

Conclusions:

  • Doxycycline-controlled HIV and SIV variants are effective tools for research and potentially safer vaccine development.
  • These variants facilitate the study of viral replication, immune responses, and viral elements like TAR and Tat.
  • Engineered viruses provide a controllable system for advancing HIV and SIV research and therapeutic strategies.