DataSheet_1_The mechanisms underlying the immune control of Zika virus infection at the maternal-fetal interface.docx

Unlike other Flaviviruses, Zika virus (ZIKV) infection during the first trimester of pregnancy causes severe pregnancy outcomes including the devastating microcephaly and diseases associated with placental dysfunctions. We have previously reported that the maternal decidua basalis, the major maternal-fetal interface, serves as a replication platform enabling virus amplification before dissemination to the fetal compartment. However, the rate of congenital infection is quite low, suggesting the presence of a natural barrier against viral infection. Using primary cells from first-trimester pregnancy samples, we investigated in this study how the maternal decidua can interfere with ZIKV infection. Our study reveals that whether through their interactions with dNK cells, the main immune cell population of the first-trimester decidua, or their production of proinflammatory cytokines, decidual stromal cells (DSCs) are the main regulators of ZIKV infection during pregnancy. We also validate the functional role of AXL as a crucial receptor for ZIKV entry in DSCs and demonstrate that targeted inhibition of ligand-receptor interaction at the early stage of the infection is effective in drastically reducing virus pathogenesis at the maternal-fetal interface. Collectively, our results provide insights into the mechanisms through which ZIKV infection and spreading can be limited. The strategy of circumventing viral entry at the maternal-fetus interface limits virus dissemination to fetal tissues, thereby preventing congenital abnormalities.</p

Additional file 7: of A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity

Figure S5. Molecular modeling of the complex between CCR5 and MVC-Sens V3. The graphic shows time series of RMSD values of the complex using as reference the input coordinates. The table indicates which constraints or restraints were imposed on the system during the simulation. bb : backbone atoms, all : all atoms, sc : side chains

Additional file 3: of A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity

Supplemental text (related to Figure 7 and additional file 4)

Additional file 1: of A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity

Figure S1. Insertion of Ala in the GPG crown impairs the replicative capacity of the HIV-1 strains Bx08 and JR-CSF. U87-CD4/CCR5 cells were infected by 10 ng Gag p24 of the indicated viral isolates and luciferase activity in the cell lysates was measured 24 h post-infection. Results are expressed as percent replication of the Ala-containing viruses relative to that of their wild-type counterparts (100%). The RLU levels for Bx08 and JR-CSF were ≈ 900000 and 700000, respectively. A representative experiment out of three independent experiments performed in triplicate is shown

Frequency of genomic alterations in the 1p/19q-co-deleted anaplastic oligodendrogliomas on the top part of the panel and non-1p/19q-co-deleted anaplastic oligodendrogliomas on the bottom part.

<p>Panel A. Genomic gain, genomic loss and uniparental disomy are indicated in red, green and blue, respectively. Panel B. High-level amplification and homozygous deletion are indicated in red and green, respectively. Panel C. Genomic breakpoints are indicated with a black dot across the genome.</p

An anaplastic oligodendroglioma with CDKN2A silencing, normal <i>CDKN2A</i> gene copy number status and copy neutral loss of heterozygosity.

<p>Panel A. Top part: Genomic profile with the copy number status. Middle part: Genomic profile with the allelic frequencies. Bottom part: The genomic profile including genomic loss (in green), normal copy number status (light blue) and copy neutral loss of heterozygosity (dark blue). Panel B. Chromosome 9 and the allelic frequencies (the arrow indicates the <i>CDKNA</i> locus). Panel C. Microsatellite analysis showing the allelic status of three markers (D9S1684, D9S171, D9S1121) in the blood DNA (top part) and paired tumor DNA (bottom part). Acquired allelic loss is observed in the tumor DNA Panel D. CDKN2A silenced using immunochemistry.</p

An anaplastic oligodendroglioma with CDKN2A expression and normal <i>CDKN2A</i> gene copy number and allelic statuses.

<p>Panel A. Top part: Genomic profile with the copy number status. Middle part: Genomic profile with the allelic frequencies. Bottom part: The genomic profile including genomic loss (in green), normal copy number status (light blue) and copy neutral loss of heterozygosity (dark blue). Panel B. Chromosome 9 and the allelic frequencies (the arrow indicates the <i>CDKNA</i> locus). Panel C. Microsatellite analysis showing the allelic status of three markers (D9S171 and D9S1121) in the blood DNA (top part) and paired tumor DNA (bottom part) Panel D. CDKN2A expression using immunochemistry.</p

Genomic alterations containing candidate genes in non 1p/19q co-deleted anaplastic oligodendrogliomas in at least two tumors (as identified by genoCN).

<p>Genomic alterations containing candidate genes in non 1p/19q co-deleted anaplastic oligodendrogliomas in at least two tumors (as identified by genoCN).</p

Heat map with genomic profiles of anaplastic oligodendrogliomas.

<p>Each column indicates a tumor. Each row indicates a genomic locus. Tumors were clustered based on the Euclidean distance between their copy number vectors. The color code on the left-upper corner indicates the genomic status: yellow, green and red indicate a normal status, loss and gain, respectively. In addition, the <i>IDH1</i> mutation (pink indicates mutated <i>IDH1</i>/<i>2</i>, while <i>IDH1</i>/<i>2</i> indicates non-mutated <i>IDH1</i>/<i>IDH2</i>), patient age (blue and pink indicate younger and older, respectively, than the median age of the entire population, 49.9 years old) and patient gender (purple indicates male, while brown indicates female) are reported at the top of the figure. The p-value on the right indicates the distribution of the variables between the 1p19q- and non-1p19q-co-deleted tumors. Panel A. 1p/19q-co-deleted anaplastic oligodendrogliomas, with chromosomes 1 and 19 centromeric breakpoints. Panel B. Non-1p/19q co-deleted anaplastic oligodendrogliomas. The legend is the same as the one used in Panel A.</p