Bovine respiratory disease (BRD) is the most significant cause of cattle morbidity and mortality worldwide. This multifactorial disease has a complex aetiology. Dogma posits a primary viral infection followed by secondary bacterial pneumonia. Bovine rhinitis B virus (BRBV) is an established aetiological agent of BRD, but little is known regarding its pathogenesis. Here, a BRD PCR panel identified 18/153 (11.8 %) lung samples and 20/49 (40.8 %) nasal swabs collected from cattle with respiratory signs as positive for BRBV, which was the most prevalent virus in nasal swabs. Primary bovine tracheal epithelial cells were used to isolate BRBV that was phylogenetically related to contemporary sequences from the USA and Mexico and genetically divergent from the previous sole BRBV isolate. To investigate virus pathogenesis, 1-week-old colostrum-deprived dairy calves were inoculated intranasally with 7.0 log₁₀TCID₅₀BRBV. Virus was isolated from nasal swabs, nasal turbinates, trachea and the brain of the challenged animals. Neutralizing antibodies were detected beginning 7 days post-inoculation and peaked at day 14.In situhybridization (ISH) localized BRBV infection in the upper respiratory ciliated epithelial and goblet cells, occasionally associated with small defects of the superficial cilia lining. Sporadically, pinpoint ISH signals were also detected in cells resembling glial cells in the cerebrum in one calf. Together, these results demonstrate the BRBV infection is highly prevalent in acute BRD samples and while the pathogenicity of BRBV is minimal with infection largely limited to the upper respiratory tract, further research is needed to elucidate a possible initiatory role in BRD.

Chikungunya virus (CHIKV) is a re-emerging arbovirus in the alphavirus genus. Upon infection, it can cause severe joint pain that can last years in some patients, significantly affecting their quality of life. Currently, there are no vaccines or anti-viral therapies available against CHIKV. Its spread to the Americas from the eastern continents has substantially increased the count of the infected by millions. Thus, there is an urgent need to identify therapeutic targets for CHIKV treatment. A potential point of intervention is the sphingosine-1-phosphate (S1P) pathway. Conversion of sphingosine to S1P is catalyzed by Sphingosine kinases (SKs), which we previously showed to be crucial pro-viral host factor during CHIKV infection. In this study, we screened inhibitors of SKs and identified a novel potent inhibitor of CHIKV infection—SLL3071511. We showed that the pre-treatment of cells with SLL3071511 in vitro effectively inhibited CHIKV infection with an EC₅₀ value of 2.91 µM under both prophylactic and therapeutic modes, significantly decreasing the viral gene expression and release of viral particles. Our studies suggest that targeting SKs is a viable approach for controlling CHIKV replication.

Antiretroviral therapy (ART) improves the quality of life for those living with the human immunodeficiency virus type one (HIV-1). However, poor compliance reduces ART effectiveness and leads to immune compromise, viral mutations, and disease co-morbidities. Here we develop a drug formulation in which a lipid-based nanoparticle (LBNP) carrying rilpivirine (RPV) is decorated with the C-C chemokine receptor type 5 (CCR5) targeting peptide. This facilitates extended drug persistence within myeloid cells. Particle delivery to viral reservoirs is tracked by positron emission tomography. The CCR5-mediated LBNP cell uptake and retention reduce HIV-1 replication in human monocyte-derived macrophages and infected humanized mice (hu mice). Focused ultrasound with microbubbles mediated blood brain barrier (BBB) disruption allows the CCR5-targeted LBNP to penetrate the BBB and reach brain myeloid cells. These findings offer a role for CCR5-targeted therapeutics in antiretroviral delivery to optimize HIV suppression.

Objectives: Amyloid-β (Aβ) plaque deposition in the brain is a principal pathological feature of both Alzheimer’s disease (AD) and progressive human immunodeficiency virus type one (HIV-1) infection. Both enable Aβ assembly and Aβ protein aggregation. The potential link between HIV-1 and AD remains uncertain, supporting the need for a reliable animal model. HIV-1 is tropic and pathogenic for humans. It does not replicate in mice. The restricted species tropism has slowed progress in basic research activities. The current study seeks to correct animal model limitations. Methods: We created an AD mouse to address the need to develop an small animal model that allows studies of viral infection by making a knock-in (KI) with the human amyloid precursor protein (APP)^KM670,671NL Swedish mutation to the mouse genome. The resulting founder mice were crossed with immunodeficient NOG (NOD. Cg-Prkdc ^scid Il2rg ^tm1Sug Tg(CMV-IL-34)1/Jic) to generate NOG/APP^KM670,671NL/IL-34 (NAIL) mice. The mice were reconstituted with human hematopoietic stem cells to generate NAIL mice with functional adaptive and innate human immune systems. Four-month-old, humanized NAIL mice were infected with HIV-1_ADA, a macrophage-tropic viral strain then evaluated for viral infection and AD pathology. Results: Productive HIV-1 infection was confirmed by plasma HIV-1 RNA levels in infected NAIL mice. The viral load increased by tenfold between day 10 and day 25 post-infection. By day 25, viral DNA confirmed the establishment of HIV-1 reservoirs in CD45+ cells from the immune tissues of infected NAIL mice. Additionally, p24 measurements in lymphoid and brain tissues of NAIL mice validated productive HIV-1 infection. Amyloid burden from infected NAIL mice was increased. Immunofluorescence staining revealed co-localization of Aβ fibrils and HLA-DR⁺ microglia in infected NAIL mice. Conclusions: These results highlight the AD-HIV model’s unique pathobiological and infectious features where the viral and immune responses can now be measured.