Leishmania donovani and HIV co-infection in vitro: Identification and characterization of main molecular players.

The incidence of Leishmania/HIV co-infection is growing and few studies detail the cellular processes and macromolecules participating in co-infection. Thus, the goal of this study was to partially describe the Leishmania/HIV co-infection events by measuring molecular and functional parameters associated with both pathogens in vitro. MT-4 cells (human T-lymphocytes), primary monocytes, and peripheral blood mononuclear cells were exposed to HIV and/or Leishmania donovani. The cytopathic effects generated by the pathogens were observed through microscopy. Viral replication was assessed by monitoring p24 protein levels and parasitic proliferation/infectivity was determined using Giemsa staining. Changes in molecular markers were evaluated by ELISA and fluorescence assays. Our results showed that our system reassembles the main parameters previously described for Leishmania/HIV co-infection in patients in terms of potentiation of parasitic and viral replication/infectivity, amplification of syncytia induction, and alterations of cell viability. In addition, an amplification in NF-κB activation, changes in CXCR4/CCR5 surface expression, and a Th1→Th2 variation in cytokine/chemokine secretion were demonstrated. Altogether, this study could contribute to gain a deep understanding of the molecular events associated with Leishmania/HIV co-infection.

SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors.

Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.