Probes for INS

An impediment to curing HIV-1 infection is the persistence of latently infected cells in ART-treated people living with HIV (PLWH). A key strategy for curing HIV-1 infection is to activate transcription and translation of latent virus using latency reversing agents (LRAs) and eliminate cells harboring reactivated virus via viral cytopathic effect or immune clearance. In this review, we provide an overview of available LRAs and their use in clinical trials. Furthermore, we describe recent data suggesting that CD8+ T cells promote HIV-1 latency in the context of ART, even in the presence of LRAs, which might at least partially explain the clinical inefficiency of previous "shock and kill" trials. Here, we propose a novel cure strategy called "unlock, shock, disarm, and kill". The general premise of this strategy is to shut down the pro-latency function(s) of CD8+ T cells, use LRAs to reverse HIV-1 latency, counteract anti-apoptotic molecules, and engage natural killer (NK) cells to mediate the killing of cells harboring reactivated latent HIV-1.

Most viruses use several entry sites and modes of transmission to infect their host (parenteral, sexual, respiratory, oro-fecal, transplacental, transcutaneous, etc.). Some of them are known to be essentially transmitted via arthropod bites (mosquitoes, ticks, phlebotomes, sandflies, etc.), and are thus named arthropod-borne viruses, or arboviruses. During the last decades, several arboviruses have emerged or re-emerged in different countries in the form of notable outbreaks, resulting in a growing interest from scientific and medical communities as well as an increase in epidemiological studies. These studies have highlighted the existence of other modes of transmission. Among them, mother-to-child transmission (MTCT) during breastfeeding was highlighted for the vaccine strain of yellow fever virus (YFV) and Zika virus (ZIKV), and suggested for other arboviruses such as Chikungunya virus (CHIKV), dengue virus (DENV), and West Nile virus (WNV). In this review, we summarize all epidemiological and clinical clues that suggest the existence of breastfeeding as a neglected route for MTCT of arboviruses and we decipher some of the mechanisms that chronologically occur during MTCT via breastfeeding by focusing on ZIKV transmission process.

Seborrheic keratoses (SKs) are benign lesions of uncertain etiology, which can develop in both genital and extra-genital locations. For genital SKs, there has been conjecture about the pathogenic role of human papillomavirus (HPV), in view of the frequent association of this virus with genital lesions. In light of the potential consequences on patient management, we investigated the relationship between HPV and SKs of the female genital tract (FGT). For this, we evaluated the current evidence on this relationship by performing an in-depth review of the literature. Furthermore, to add to the evidence on this association, we investigated the presence of HPV in a series of vulvar SKs (n=15), using a novel multimodal approach. This involved whole tissue section-polymerase chain reaction (WTS-PCR) using SPF10-DEIA-LipA25 for HPV detection and genotyping. In addition, immunohistochemistry (IHC) was performed with cellular biomarkers p16 and MIB-1, and viral biomarker E4, to augment HPV-testing. Finally, laser-capture microdissection-PCR (LCM-PCR) was performed to locate HPV to specific lesional cells, and to rule out incidental detection of resident HPV with WTS-PCR. Our findings from the literature review, as well as, the case-series are presented.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel type b coronavirus responsible for the COVID-19 pandemic. With over 224 million confirmed infections with this virus and more than 4.6 million people dead because of it, it is critically important to define the immunological processes occurring in the human response to this virus and pathogenetic mechanisms of its deadly manifestation. This perspective focuses on the contribution of the recently discovered interaction of SARS-CoV-2 Spike protein with neuropilin 1 (NRP1) receptor, NRP1 as a virus entry receptor for SARS-CoV-2, its role in different physiologic and pathologic conditions, and the potential to target the Spike-NRP1 interaction to combat virus infectivity and severe disease manifestations.

The field of infectious diseases currently takes a reactive approach, treating infections as they present in patients. Although certain populations are known to be at greater risk of developing infection (e.g., immunocompromised), we lack a systems approach to define the true risk of future infection for a patient. Guided by impressive gains in -omics technologies, future strategies to infectious diseases should take a precision approach to infection through identification of patients at intermediate and high-risk of infection and deploy targeted preventative measures (i.e., prophylaxis). The advances of high-throughput immune profiling by multiomics approaches (i.e., transcriptomics, epigenomics, metabolomics, proteomics) holds the promise to identify patients at increased risk of infection and enable risk-stratifying approaches to be applied in the clinic. Integration of patient-specific data using machine learning improves the effectiveness of prediction, providing the necessary technologies needed to propel the field of infectious diseases medicine into the era of personalized medicine.

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, causes neonatal pig acute gastrointestinal infection with a characterization of severe diarrhea, vomiting, high morbidity, and high mortality, resulting in tremendous damages to the swine industry. Neither specific antiviral drugs nor effective vaccines are available, posing a high priority to screen antiviral drugs. The aim of this study is to investigate anti-PEDV effects of carbazole alkaloid derivatives. Eighteen carbazole derivatives (No.1 to No.18) were synthesized, and No.5, No.7, and No.18 were identified to markedly reduce the replication of enhanced green fluorescent protein (EGFP) inserted-PEDV, and the mRNA level of PEDV N. Flow cytometry assay, coupled with CCK8 assay, confirmed No.7 and No.18 carbazole derivatives displayed high inhibition effects with low cell toxicity. Furthermore, time course analysis indicated No.7 and No.18 carbazole derivatives exerted inhibition at the early stage of the viral life cycle. Collectively, the analysis underlines the benefit of carbazole derivatives as potential inhibitors of PEDV, and provides candidates for the development of novel therapeutic agents.