Viral gene drive in herpesviruses
1Buck Institute for Research on Aging, Novato, CA, 94945, USA. mwalter@buckinstitute.org.
Nature Communications
|September 28, 2020
Summary
Scientists engineered a novel gene drive system capable of spreading traits through virus populations, specifically demonstrating its effectiveness in human cytomegalovirus. This breakthrough offers a new strategy for potentially suppressing viral infections by targeting essential viral replication sequences.
Area of Science:
- Virology
- Molecular Biology
- Genetic Engineering
Background:
- Gene drives are engineered genetic elements designed for high-frequency propagation within populations.
- Existing gene drive technologies are primarily limited to sexual organisms and rely on sexual reproduction.
- The potential application of gene drives in non-organismal systems, such as viruses, remains largely unexplored.
Purpose of the Study:
- To investigate the feasibility of a gene drive system in DNA viruses, specifically herpesviruses.
- To demonstrate the transmission and propagation of an engineered gene drive sequence within a viral population.
- To explore the potential of viral gene drives as a novel antiviral therapeutic strategy.
Main Methods:
- Development of a gene drive system designed for propagation in viral populations.
- Experimental transmission of the gene drive sequence between distinct strains of human cytomegalovirus (human herpesvirus 5).
- Cell culture experiments to assess the efficiency of gene drive viruses in targeting and replacing wildtype viral populations.
Main Results:
- Successful transmission of an engineered gene drive sequence between different strains of human cytomegalovirus.
- Demonstration that gene drive viruses can efficiently target and outcompete wildtype viral populations in vitro.
- Gene drive viruses targeting essential replication sequences showed potential for suppressing viral infection.
Conclusions:
- This study provides the first proof of principle for a functional gene drive system in viruses.
- Viral gene drives represent a novel platform for genetic modification of viral populations.
- The findings suggest a potential new avenue for developing antiviral therapies by leveraging gene drive technology.
Related Concept Videos
Size and Structure of Viral Genomes
497
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...
497
Retroviruses
14.3K
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’...
14.3K
Retrovirus Life Cycles
48.8K
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...
48.8K
Mechanisms of Retrovirus-induced Cancers
6.6K
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...
6.6K
Horizontal Gene Transfer
935
Horizontal gene transfer (HGT) is a process where genetic material moves between organisms within the same generation, unlike vertical gene transfer, which occurs from parent to offspring. HGT plays a crucial role in microbial evolution, adaptation, and survival, particularly in shared environments like the human gut.Mobile genetic elements such as plasmids, prophages, integrons, insertion sequences, and transposons facilitate this process. HGT occurs through three primary mechanisms:...
935
Viruses with RNA Genomes
514
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...
514


