Good news!
"The findings, published in PLOS Pathogens, could lead to new treatments that don’t just suppress HIV-infected cells, but kill them. That would be a key step toward finally curing HIV. ...
[researchers] looked at a type of sugar found on the surface of HIV cells called sialic acid. These sugars can trigger inhibitors on disease-fighting "killer" immune cells, shutting them down before they attack. ... that these HIV-infected cells are covering themselves with these sugars to evade immune surveillance ...
[researchers] looked at a type of sugar found on the surface of HIV cells called sialic acid. These sugars can trigger inhibitors on disease-fighting "killer" immune cells, shutting them down before they attack. ... that these HIV-infected cells are covering themselves with these sugars to evade immune surveillance ...
The researchers used an enzyme that removed the sialic acid. This caused the immune cells to attack and destroy the HIV.
"The killer cells become a super killer for the HIV-infected cells," ...
Current treatments can reduce HIV to undetectable levels, but they can’t eradicate it entirely. The disease typically returns quickly when treatment stops. ..."
From the abstract:
"Siglec-9 is an MHC-independent inhibitory receptor expressed on a subset of natural killer (NK) cells. Siglec-9 restrains NK cytotoxicity by binding to sialoglycans (sialic acid-containing glycans) on target cells. Despite the importance of Siglec-9 interactions in tumor immune evasion, their role as an immune evasion mechanism during HIV infection has not been investigated. Using in vivo phenotypic analyses, we found that Siglec-9+ CD56dim NK cells, during HIV infection, exhibit an activated phenotype with higher expression of activating receptors and markers (NKp30, CD38, CD16, DNAM-1, perforin) and lower expression of the inhibitory receptor NKG2A, compared to Siglec-9- CD56dim NK cells. We also found that levels of Siglec-9+ CD56dim NK cells inversely correlate with viral load during viremic infection and CD4+ T cell-associated HIV DNA during suppressed infection. Using in vitro cytotoxicity assays, we confirmed that Siglec-9+ NK cells exhibit higher cytotoxicity towards HIV-infected cells compared to Siglec-9- NK cells. These data are consistent with the notion that Siglec-9+ NK cells are highly cytotoxic against HIV-infected cells. However, blocking Siglec-9 enhanced NK cells’ ability to lyse HIV-infected cells, consistent with the known inhibitory function of the Siglec-9 molecule. Together, these data support a model in which the Siglec-9+ CD56dim NK subpopulation is highly cytotoxic against HIV-infected cells even whilst being restrained by the inhibitory effects of Siglec-9. To harness the cytotoxic capacity of the Siglec-9+ NK subpopulation, which is dampened by Siglec-9, we developed a proof-of-concept approach to selectively disrupt Siglec/sialoglycan interactions between NK and HIV-infected cells. We achieved this goal by conjugating Sialidase to several HIV broadly neutralizing antibodies. These conjugates selectively desialylated HIV-infected cells and enhanced NK cells’ capacity to kill them. ..."
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