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Cellular fatty acid synthase is required for late stages of HIV-1 replication

Overview of attention for article published in Retrovirology, September 2017
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Mentioned by

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4 tweeters

Citations

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11 Dimensions

Readers on

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15 Mendeley
Title
Cellular fatty acid synthase is required for late stages of HIV-1 replication
Published in
Retrovirology, September 2017
DOI 10.1186/s12977-017-0368-z
Pubmed ID
Authors

Manjusha M. Kulkarni, Annette N. Ratcliff, Menakshi Bhat, Yazan Alwarawrah, Philip Hughes, Jesus Arcos, David Loiselle, Jordi B. Torrelles, Nicholas T. Funderburg, Timothy A. Haystead, Jesse J. Kwiek

Abstract

Like all viruses, HIV-1 relies on host systems to replicate. The human purinome consists of approximately two thousand proteins that bind and use purines such as ATP, NADH, and NADPH. By virtue of their purine binding pockets, purinome proteins are highly druggable, and many existing drugs target purine-using enzymes. Leveraging a protein affinity media that uses the purine-binding pocket to capture the entire purinome, we sought to define purine-binding proteins regulated by HIV-1 infection. Using purinome capture media, we observed that HIV-1 infection increases intracellular levels of fatty acid synthase (FASN), a NADPH-using enzyme critical to the synthesis of de novo fatty acids. siRNA mediated knockdown of FASN reduced HIV-1 particle production by 80%, and treatment of tissue culture cells or primary PBMCs with Fasnall, a newly described selective FASN inhibitor, reduced HIV-1 virion production by 90% (EC50 = 213 nM). Despite the requirement of FASN for nascent virion production, FASN activity was not required for intracellular Gag protein production, indicating that FASN dependent de novo fatty acid biosynthesis contributes to a late step of HIV-1 replication. Here we show that HIV-1 replication both increases FASN levels and requires host FASN activity. We also report that Fasnall, a novel FASN inhibitor that demonstrates anti-tumor activity in vivo, is a potent and efficacious antiviral, blocking HIV-1 replication in both tissue culture and primary cell models of HIV-1 replication. In adults, most fatty acids are obtained exogenously from the diet, thus making FASN a plausible candidate for pharmacological intervention. In conclusion, we hypothesize that FASN is a novel host dependency factor and that inhibition of FASN activity has the potential to be exploited as an antiretroviral strategy.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 33%
Student > Master 3 20%
Unspecified 2 13%
Student > Bachelor 2 13%
Student > Doctoral Student 1 7%
Other 2 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 40%
Unspecified 3 20%
Immunology and Microbiology 3 20%
Nursing and Health Professions 1 7%
Agricultural and Biological Sciences 1 7%
Other 1 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 November 2017.
All research outputs
#6,540,882
of 12,119,647 outputs
Outputs from Retrovirology
#317
of 598 outputs
Outputs of similar age
#114,724
of 270,609 outputs
Outputs of similar age from Retrovirology
#5
of 11 outputs
Altmetric has tracked 12,119,647 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 598 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 270,609 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.