How SAMHD1 changes our view of viral restriction

Recent studies have uncovered sterile alpha motif and HD domain 1 (SAMHD1) as the restriction factor that blocks HIV-1 replication in myeloid cells. In contrast to previously identified HIV-1 restriction factors, SAMHD1 does not meet a countermeasure developed by HIV-1. However, HIV-2 and certain simian immunodeficiency virus (SIV) strains express the auxiliary protein Vpx that potently blocks SAMHD1. It is therefore perplexing why this function has been lost or not acquired during the course of lentiviral evolution. This article summarizes the similarities and differences between SAMHD1 and other HIV-1 restriction factors, while highlighting the new questions that are emerging about the crosstalk between restriction factors and innate immune responses.     

Diabetes prevalence is associated with obesity,hypertension, dyslipidemia,and sociodemographic factors in adults living in Casablanca-Settat and Rabat-Sale-Kenitra regions,Morocco

International Journal of Diabetes in Developing Countries - Diabetes is increasing at an alarming rate worldwide, but little is known about its risk factors in Morocco. This study aimed to...     

Traitement par radiochimiothérapie d’un carcinome endocrine indifférencié du canal anal : à propos d’un cas

Undifferentiated endocrine carcinoma of anal canal is a rare cancer with a poor prognosis linked to the frequency of occurrence of hepatic and pulmonary metastasis. Most patients have metastatic disease at the time of diagnosis. The locoregional treatment is generally surgical as abdominopelvic excision, but this one is not obvious taking into consideration the mutilation which it does impose in a context of strong metastatic risk and death in the near short term. We report one case of undifferentiated endocrine carcinoma localized in the anal canal, and treated by external radiotherapy and a chemotherapy regimen combining etoposide plus cisplatine resulting in prolonged complete local remission and preventing extended surgical excision. An important place could thus be given to the non surgical treatment combining radiotherapy and chemotherapy.     

Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1

Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism. CCR5 is the major macrophage-tropic coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1-CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the early in vivo course of HIV-1 disease.     

Semaphorin 3A receptor inhibitor as a novel therapeutic to promote innervation of bioengineered teeth

The sensory innervation of the dental pulp is essential for tooth function and protection. It is mediated by axons originating from the trigeminal ganglia and is spatio‐temporally regulated. We have previously shown that the innervation of bioengineered teeth can be achieved only under immunosuppressive conditions. The aim of this study was to develop a model to determine the role of Semaphorin 3A (Sema3A) in the innervation of bioengineered teeth. We first analysed innervation of the dental pulp of mandibular first molars in newborn (postnatal day 0: PN0) mice deficient for Sema3A (Sema3A^?/?), a strong inhibitor of axon growth. While at PN0, axons detected by immunostaining for peripherin and NF200 were restricted to the peridental mesenchyme in Sema3A^+/+ mice, they entered the dental pulp in Sema3A^?/? mice. Then, we have implanted cultured teeth obtained from embryonic day‐14 (E14) molar germs of Sema3A^?/? mice together with trigeminal ganglia. The dental pulps of E14 cultured and implanted Sema3A^?/? teeth were innervated, whereas the axons did not enter the pulp of E14 Sema3A^+/+ cultured and implanted teeth. A “Membrane Targeting Peptide NRP1,” suppressing the inhibitory effect of Sema3A, has been previously identified. The injection of this peptide at the site of implantation allowed the innervation of the dental pulp of bioengineered teeth obtained from E14 dental dissociated mesenchymal and epithelial cells reassociations of ICR mice. In conclusion, these data show that inhibition of only one axon repellent molecule, Sema3A, allows for pulp innervation of bioengineered teeth.