CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: In conclusion, our experiments supported the beneficial role of LILRA3 in virus infections, in particular for ssRNA viruses, like HIV, that engage TLR8. These findings indicate considerable potential for exploring the use of LILRA3 in the treatment of virus infection.

WEDNESDAY, FEBRUARY 25, 2015 Session P-C4 Poster Session

Poster Abstracts

Poster Hall

2:30 pm– 4:00 pm Monocytes, Dendritic Cells, and Neutrophils 283 Siglec-1 on Monocytes FromUntreated HIV-1 – Infected Patients Enhances HIV-1 Transfer Maria Pino ; Susana Benet; Itziar Erkizia; Judith Dalmau; Dan Ouchi; Bonaventura Clotet; Javier Martínez-Picado; Nuria Izquierdo-Useros IrsiCaixa Institute for AIDS Research, Badalona, Spain

Background: The IFN α -inducible receptor Siglec-1 (CD169) is expressed on myeloid cells and recognizes HIV-1 membrane gangliosides, enhancing viral uptake and cell-to-cell transmission. Moreover, Siglec-1 is upregulated on monocytes of HIV-1-infected-individuals with high viral loads. However, if Siglec-1 expressed on monocytes from HIV-1-infected patients mediates viral transmission is still unknown. Here, we aim to study the role of Siglec-1 in HIV-1 transfer on primary monocytes isolated from HIV-1 infected patients. Methods: We assessed Siglec-1 expression on monocytes from HIV-1-infected individuals before and after antiretroviral treatment and IFN α -treated monocytes from seronegative donors by FACS. P24 Gag ELISA and a luciferase-reporter cell line were used to assess monocyte-mediated HIV-1 uptake and transmission. mAb α -Siglec-1 was used to study specific HIV-1 recognition via Siglec-1. Siglec-1 induction was analyzed by FACS on myeloid cells cultured with plasmas from HIV-1-infected individuals, and blocked with the type I IFN recombinant protein B18R. Statistical analyses were performed using paired t-test ( P ) and Pearson correlation ( ρ ). Results: IFN α -treated monocytes have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition. Siglec-1 expression was higher on monocytes isolated before antiretroviral treatment that also exhibited a higher HIV-1 uptake and HIV-1 transmission capacity compared to monocytes obtained under suppressive therapy ( P ≤ 0.0117). Consistently, plasmas of untreated HIV-1-infected individuals triggered higher Siglec-1 expression on myeloid cells compared to plasmas from the same individuals, but obtained after antiretroviral treatment. Furthermore, Siglec-1 induction could be blocked by the neutralizing/decoy type I IFN receptor B18R ( P <0.0001). Finally, we found a positive correlation between Siglec-1 expression levels on isolated monocytes from treatment-naïve patients and i) HIV-1 uptake ( ρ = 0.8), ii) HIV-1 trans-infection capacity ( ρ =0.78) and iii) plasma viral load ( ρ = 0.66). Conclusions: These results indicate that in vivo , Siglec-1 expression on peripheral blood monocytes is upregulated by HIV-1 infection, but normalizes after effective antiretroviral treatment. Soluble activation factors from plasma of these patients induced Siglec-1 expression on myeloid cells via type I IFN receptor signaling. Furthermore, Siglec-1 on monocytes enhances HIV-1 cell-to-cell transmission, indicating that this receptor could impact HIV-1 pathogenesis.

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CROI 2015