Sandflies are flying, biting, blood-sucking arthropods known to be vectors of the etiological agent of Leishmaniasis, a zoonotic disease that can be fatal for both animals and humans. This disease represents a Global Health problem due to its presence in all countries surrounding the Mediterranean Basin and in most countries in South and North America (areas where the disease is considered endemic). Although sandflies are known to be the vector of several Leishmania species, little is known about their vector capacity for other zoonotic pathogens, such as Bartonella, in the Mediterranean Basin. This genus of bacteria is known to cause Bartonellosis, an infectious, zoonotic disease that can cause Carrión's disease, trench fever, cat-scratch disease, neurological disorders, and more. Beyond being able to transmit Bartonella bacilliformis (a potential fatal pathogen in humans), some preliminary data generated by the Intracellular Pathogens Research Laboratory showed that other Bartonella species (such as B. henselae, B. bovis, and B. merieux) are present in sandflies. This study focuses on assessing the prevalence of different Leishmania and Bartonella species in sandflies collected from Italy, Portugal, and Iraq. The information gathered by this work, via DNA extraction, qualitative polymerase chain reaction (qPCR) assays, and conventional PCR assays, will help to assess the potential risks of zoonotic infections by exposure to sandflies. Our preliminary PCR data show positive DNA results for both Leishmania and Bartonella DNA in sandflies from each of the three targeted countries, and we are continuing to test sandfly DNA samples using PCR.

Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus linked to several diseases, including Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. It establishes lifelong infection by alternating latent and lytic cycles, permitting immune evasion and host defense exploitation. Since KSHV is primarily transmitted via a salivary-mucosal route, preventing infections at mucosal surfaces is critical. Mucosal vaccines aim to elicit immune protection at entry sites, such as the oral and nasal cavity, with intranasal immunization conferring to oral protection through shared mucosal immune trafficking and secretory IgA in saliva. Despite this potential, few studies have examined mucosal vaccines against KSHV, highlighting a gap in prevention strategies. Here, we evaluated lipid nanoparticles (LNPs) carrying KSHV open reading frame 4 (ORF4) mRNA, which encodes a complement control protein, for intranasal immunization. In a murine model, intranasal immunization was well tolerated and elicited systemic and mucosal antibody responses. Indirect ELISA of serum and saliva detected ORF4-specific IgA and IgG, indicating activation of both mucosal and systemic immunity. These findings underscore the potential for mRNA-LNP vaccination delivered intranasally to induce mucosal responses against KSHV and reduce KSHV-associated diseases.

Alzheimer’s disease (AD) is a progressive neurodegenerative condition associated with amyloid-beta plaques. Accumulation of amyloid-beta plaques induces activation of myeloid cells, which can damage neurons and drive cognitive decline in AD patients. Recent evidence suggests that gut microbiota and their metabolites can influence AD progression as they can reduce neuroinflammation and stabilize metabolism in neurodegenerative diseases. This study investigated whether the bacterium Akkermansia muciniphila or a cocktail of the microbial metabolites butyrate, beta-hydroxybutyrate, and ursodeoxycholic acid, can effectively treat AD symptoms in a mouse model. We hypothesized that both treatment groups would exhibit reduced myeloid cell levels in the hippocampus. We treated mice with either microbes or the metabolite cocktail for three months and measured their neuroinflammation. Contrary to our initial hypothesis, the administration of A. muciniphila and the metabolite cocktail did not significantly reduce neuroinflammation. However, these results narrow the search for the precise microbial signals that effectively inhibit neuroinflammation in AD. Ultimately, this research aims to establish an accessible microbiome-based strategy to slow AD progression and address health disparities in disproportionately affected communities where high-cost clinical interventions are out of reach.

Human Immunodeficiency Virus Type 1 (HIV-1) relies on host nuclear export receptor XPO1 to transport unspliced and partially spliced viral RNAs from the nucleus to the cytoplasm, a vital step in viral replication. This process is mediated by the viral Rev protein, which multimerizes at the Rev Response Element (RRE) and recruits XPO1 via the Rev-encoded Nuclear Export Signal (NES). Previous research using purified protein in vitro suggests that XPO1 forms dimeric complexes in an RRE- and Rev-dependent manner. However, whether XPO1 dimerizes in cells during HIV-1 infection and represents a viable target for antiviral therapy has yet to be demonstrated. We hypothesize that XPO1 multimerization occurs in living cells and is enhanced by the presence of Rev and the RRE. To address this question, we established a split nanoluciferase (Nluc) complementation assay in which XPO1 proteins are expressed from plasmids and fused to complementary Large BiT (LgBiT) and Small BiT (SmBiT) luciferase fragments. When two XPO1 molecules are brought into proximity through protein-protein interactions, the fragments reconstitute an active Nluc enzyme that, upon substrate addition, produces a luminescent signal. This system enables quantitative detection of XPO1-XPO1 interactions in living cells. Using this approach, we will determine whether XPO1 dimerization depends on the presence of Rev, the RRE, and specific structural elements of predicted Rev-RRE complexes. By comparing Rev with mutants defective in RNA binding or in Rev-Rev interactions, and with RRE-deletion variants, we will determine how RNA structures influence XPO1 dimerization and whether this correlates with Rev/RRE-dependent gene expression.