Related Experiment Video
Updated: Aug 19, 2025
07:18
High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing
Published on: January 22, 2019
5.9K
HIV-1 replication and latency are balanced by mTOR-driven cell metabolism
Jacqueline M Crater1, Douglas F Nixon1, Robert L Furler O'Brien1
1Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, United States.
Frontiers in Cellular and Infection Microbiology
|December 5, 2022
Summary
Human Immunodeficiency virus type 1 (HIV-1) hijacks host cell metabolism, particularly the mTOR pathway, to fuel viral replication and production. Understanding these metabolic connections is key to developing new HIV treatments and targeting latent reservoirs.
Area of Science:
- Virology
- Cellular Metabolism
- Immunology
Background:
- Human Immunodeficiency virus type 1 (HIV-1) replication is critically dependent on host cell metabolic processes.
- Activated T cells provide an optimal metabolic environment for HIV-1 entry, reverse transcription, and integration.
- The mechanistic target of rapamycin (mTOR) pathway is central to HIV-1's manipulation of host metabolism.
Purpose of the Study:
- To elucidate the intricate relationship between host cell metabolism and HIV-1 pathogenesis.
- To explore how metabolic pathways influence viral replication, latency, and reactivation.
- To identify potential therapeutic targets within host metabolic pathways for HIV-1 cure strategies.
Main Methods:
- Analysis of host cell metabolic pathways co-opted by HIV-1 proteins.
- Investigation of the role of mTOR, HIF-1α, and Myc signaling in altering host metabolism.
- Examination of metabolic requirements across different stages of the HIV-1 life cycle, including early replication and viral budding.
- Assessment of metabolic contributions to proviral epigenetics and latency.
Main Results:
- HIV-1 utilizes host metabolic pathways, including glycolysis and the pentose phosphate pathway, for essential functions like dNTP synthesis during reverse transcription.
- Fatty acid synthesis is crucial for producing lipids required for viral budding and virion production.
- mTOR signaling, alongside HIF-1α and Myc, reshapes host metabolism to favor viral replication.
- Metabolic factors like Acetyl-CoA and methyl groups, supplied by the TCA cycle and amino acid uptake, influence proviral epigenetics, impacting active and latent infection.
Conclusions:
- Host cell metabolism, particularly regulated by mTOR, is indispensable for HIV-1 replication, latency, and reactivation.
- Targeting host metabolic pathways presents a promising avenue for novel HIV-1 therapeutics and strategies to eradicate latent viral reservoirs.
More Related Videos
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
01:22PI3K/mTOR/AKT Signaling Pathway
3.8K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.8K
01:26Size and Structure of Viral Genomes
99
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...
99
01:10Retrovirus Life Cycles
46.5K
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...
46.5K
01:29Viruses with RNA Genomes
84
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...
84
01:51Mechanisms of Retrovirus-induced Cancers
5.2K
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...
5.2K