Efficacy assessment of antiretroviral drugs against equine infectious anemia virus in vitro.

Equine infectious anemia virus (EIAV) is an equine lentivirus related to human immunodeficiency virus type 1 (HIV-1). Both viruses are related among the Retroviridae family, but their clinical manifestations are different as EIAV causes a long persistent infection with no progressive immune dysfunction in most cases. Today, no treatment is approved against EIAV, contrary to HIV-1, manageable through antiretroviral therapy, known as HAART (highly active antiretroviral therapy) or cART (combination antiretroviral therapy).

Undetection of vector-borne viruses in equids of Galapagos Islands.

Domestic species, including equids, were introduced in the Galapagos Islands in the XIX century. Equine vector-borne diseases are circulating in South America but their occurrence in the Galapagos Island was unknown. The objective of this study was to detect the occurrence of West Nile virus (WNV), Usutu virus (USUV) and equine infectious anemia virus (EIAV) in the four Galapagos Islands raising equids if they were present at a prevalence >1%.

The first report of triple anthelmintic resistance on a French Thoroughbred stud farm.

This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March-April and in November-December) and the efficacy of pyrantel in one group once (in May-June).

Prevalence and seasonal dynamic of gastrointestinal parasites in equids in France during two years.

Grazing equids are constantly exposed to three clinically important gastrointestinal parasites (small strongyles/cyathostomins, Anoplocephala spp. and Parascaris spp.).

Equine influenza outbreak in Eastern of Algeria in 2021: The first introduction of Florida Clade 1 to Maghreb area.

We have performed an equine influenza (EI) serological study of the equine population in Algeria by testing 298 serum samples collected between February and August 2021 from 5 provinces. The results were obtained performing an NP-ELISA. Our results revealed that 49.

Serological evidence of circulation of West Nile virus in equids in Algerian eastern drylands and its epidemiological risk factors.

In order to determine the prevalence of equine infectious anemia virus (EIAV), Usutu virus (USUV), and West Nile virus (WNV) in eastern Algerian drylands, 340 sera from distinct equids have been collected from 2015 to 2017. Serological analysis for the presence of antibodies against EIAV and flaviviruses was performed using commercially available ELISAs. Sera detected positive, doubtful, or negative close to the doubtful threshold in flavivirus ELISA were tested by the virus neutralization test (VNT), using WNV and USUV strains.

A Bioluminescent 3CL Activity Assay to Monitor SARS-CoV-2 Replication and Identify Inhibitors.

Our therapeutic arsenal against viruses is very limited and the current pandemic of SARS-CoV-2 highlights the critical need for effective antivirals against emerging coronaviruses. Cellular assays allowing a precise quantification of viral replication in high-throughput experimental settings are essential to the screening of chemical libraries and the selection of best antiviral chemical structures. To develop a reporting system for SARS-CoV-2 infection, we generated cell lines expressing a firefly luciferase maintained in an inactive form by a consensus cleavage site for the viral protease 3CL of coronaviruses, so that the luminescent biosensor is turned on upon 3CL expression or SARS-CoV-2 infection.

Metabolic plasticity of HIV-specific CD8 T cells is associated with enhanced antiviral potential and natural control of HIV-1 infection.

Spontaneous control of human immunodeficiency virus (HIV) is generally associated with an enhanced capacity of CD8 T cells to eliminate infected CD4 T cells, but the molecular characteristics of these highly functional CD8 T cells are largely unknown. In the present study, using single-cell analysis, it was shown that HIV-specific, central memory CD8 T cells from spontaneous HIV controllers (HICs) and antiretrovirally treated non-controllers have opposing transcriptomic profiles. Genes linked to effector functions and survival are upregulated in cells from HICs.

Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors.

RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids.

Antiapoptotic Clone 11-Derived Peptides Induce Death of CD4 T Cells Susceptible to HIV-1 Infection.

HIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4 T cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of antiapoptotic clone 11 (AAC-11), an antiapoptotic factor upregulated in many cancers, increased with progressive CD4 T cell memory differentiation in association with the expression of cell cycle, activation, and metabolism genes and was correlated with susceptibility to HIV-1 infection.

Cross-talk between SUMOylation and ISGylation in response to interferon.

Interferon (IFN) plays a central role in regulating host immune response to viral pathogens through the induction of IFN-Stimulated Genes (ISGs). IFN also enhances cellular SUMOylation and ISGylation, though the functional interplay between these modifications remains unclear. Here, we used a system-level approach to profile global changes in protein abundance in SUMO3-expressing cells stimulated by IFNα.

Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4 T Cells and Offers an Opportunity to Tackle Infection.

HIV persists in long-lived infected cells that are not affected by antiretroviral treatment. These HIV reservoirs are mainly located in CD4 T cells, but their distribution is variable in the different subsets. Susceptibility to HIV-1 increases with CD4 T cell differentiation.

Cellular Determinants of HIV Persistence on Antiretroviral Therapy.

The era of antiretroviral therapy has made HIV-1 infection a manageable chronic disease for those with access to treatment. Despite treatment, virus persists in tissue reservoirs seeded with long-lived infected cells that are resistant to cell death and immune recognition. Which cells contribute to this reservoir and which factors determine their persistence are central questions that need to be answered to achieve viral eradication.

p21 Restricts HIV-1 in Monocyte-Derived Dendritic Cells through the Reduction of Deoxynucleoside Triphosphate Biosynthesis and Regulation of SAMHD1 Antiviral Activity.

HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability of deoxynucleoside triphosphates (dNTPs), which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during the cell cycle and depend on the balance between dNTP biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear.

Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility.

SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation.

Contribution of oligomerization to the anti-HIV-1 properties of SAMHD1.

Background: SAMHD1 is a restriction factor that potently blocks infection by HIV-1 and other retroviruses. We have previously demonstrated that SAMHD1 oligomerizes in mammalian cells by immunoprecipitation. Here we investigated the contribution of SAMHD1 oligomerization to retroviral restriction.

The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6.

Background: Expression of the cellular karyopherin TNPO3/transportin-SR2/Tnp3 is necessary for HIV-1 infection. Depletion of TNPO3 expression in mammalian cells inhibits HIV-1 infection after reverse transcription but prior to integration.

Results: This work explores the role of cleavage and polyadenylation specificity factor subunit 6 (CPSF6) in the ability of TNPO3-depleted cells to inhibit HIV-1 infection.

Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication.

The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1.

Contribution of SAM and HD domains to retroviral restriction mediated by human SAMHD1.

The human SAMHD1 protein is a novel retroviral restriction factor expressed in myeloid cells. Previous work has correlated the deoxynucleotide triphosphohydrolase activity of SAMHD1 with its ability to block HIV-1 and SIV(mac) infection. SAMHD1 is comprised of the sterile alpha motif (SAM) and histidine-aspartic (HD) domains; however the contribution of these domains to retroviral restriction is not understood.

Contribution of SUMO-interacting motifs and SUMOylation to the antiretroviral properties of TRIM5α.

Recent findings suggested that the SUMO-interacting motifs (SIMs) present in the human TRIM5α (TRIM5α(hu)) protein play an important role in the ability of TRIM5α(hu) to restrict N-MLV. Here we explored the role of SIMs in the ability of rhesus TRIM5α (TRIM5α(rh)) to restrict HIV-1, and found that TRIM5α(rh) SIM mutants IL376KK (SIM1mut) and VI405KK (SIM2mut) completely lost their ability to block HIV-1 infection. Interestingly, these mutants also lost the recently described property of TRIM5α(rh) to shuttle into the nucleus.

Reduced connexin43 expression correlates with c-Src activation, proliferation, and glucose uptake in reactive astrocytes after an excitotoxic insult.

In diverse brain pathologies, astrocytes become reactive and undergo profound phenotypic changes. Connexin43 (Cx43), the main gap junction channel-forming protein in astrocytes, is one of the proteins modified in reactive astrocytes. Downregulation of Cx43 in cultured astrocytes activates c-Src, promotes proliferation, and increases the rate of glucose uptake; however, so far there have been no studies examining whether this cascade of events takes place in reactive astrocytes.

Role of SAMHD1 nuclear localization in restriction of HIV-1 and SIVmac.

Background: SAMHD1 is a nuclear protein that blocks lentiviral infection before reverse transcription in macrophages and dendritic cells. The viral accessory protein Vpx overcomes the SAMHD1-mediated lentiviral block by inducing its proteasomal degradation.

Results: Here, we identified the nuclear localization signal (NLS) of SAMHD1, and studied its contribution to restriction of HIV-1 and SIVmac.

TNPO3 is required for HIV-1 replication after nuclear import but prior to integration and binds the HIV-1 core.

TNPO3 is a nuclear importer required for HIV-1 infection. Here, we show that depletion of TNPO3 leads to an HIV-1 block after nuclear import but prior to integration. To investigate the mechanistic requirement of TNPO3 in HIV-1 infection, we tested the binding of TNPO3 to the HIV-1 core and found that TNPO3 binds to the HIV-1 core.

HIF-1 and c-Src mediate increased glucose uptake induced by endothelin-1 and connexin43 in astrocytes.

In previous work we showed that endothelin-1 (ET-1) increases the rate of glucose uptake in astrocytes, an important aspect of brain function since glucose taken up by astrocytes is used to supply the neurons with metabolic substrates. In the present work we sought to identify the signalling pathway responsible for this process in primary culture of rat astrocytes. Our results show that ET-1 promoted an increase in the transcription factor hypoxia-inducible factor-1α (HIF-1α) in astrocytes, as shown in other cell types.