SAMHD1 was previously identified as a critical post-entry restriction factor to HIV-1 infection in myeloid dendritic cells (DC). Here we show that SAMHD1 is also expressed in epidermis- isolated Langerhans Cells (LC) but degradation of SAMHD1 does not rescue HIV-1 or VSV- G-pseudotyped lentivectors infection in LC. Strikingly, using Langerhans cells model systems (MuLC, MDLC and freshly isolated epidermal LC), we characterize previously unreported post-entry restriction activity to HIV-1 in these cells, which acts at HIV-1 reverse transcription, but remains independent of restriction factors SAMHD1 and MX2. We demonstrate that TGFβ signalling confers this potent HIV-1 restriction in MDLC during their differentiation and blocking of SMAD2 signalling in MDLC restores cells infectivity. Interestingly, maturation of MDLC with a TLR2 agonist or TNFα significantly increases cells susceptibility to HIV-1 infection, which may explain why HIV-1 acquisition is increased during co-infection with sexually transmitted infections (STIs). In conclusion, we report a SAMHD1-independent post- entry restriction in MDLC and LC isolated from epidermis, which inhibits HIV-1 replication. A better understanding of HIV-1 restriction and propagation from LC to CD4(+) T cells may help in the development of new microbicides or vaccines to curb HIV-1 infection at its earliest stages during mucosal transmission.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Veterinary Science and Veterinary Medicine
1
3%
Other
5
15%
Unknown
8
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 06 July 2016.
All research outputs
#17,286,379
of 25,374,647 outputs
Outputs from Journal of Investigative Dermatology
#7,395
of 8,996 outputs
Outputs of similar age
#237,458
of 367,294 outputs
Outputs of similar age from Journal of Investigative Dermatology
#70
of 98 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,996 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
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We're also able to compare this research output to 98 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.
