Abdellatif, A. | bioRxiv Science

bioRxiv2026

CypA is a molecular barrier to HIV emergence from Eastern chimpanzees

Of the two lineages of lentivirus that endemically infect chimpanzees, only one has served as a source of infections in hu-mans. Using HIV-CRISPR screening, we identify factors that limit the replication of lentivirus from Eastern chimpanzees. We find that CypA restricts nonzoonotic Eastern chimpanzee lentivirus due to a unique feature encoded in capsid. The ability of CypA to restrict lentivirus replication is surprising given that CypA is a host factor exploited by HIV to promote its replica-tion. The selective ability of CypA to restrict this virus provides a molecular explanation as to why lentivirus from Eastern Chimpanzees has never been observed to infect humans. Our work has important implications for understanding the origins of HIV-1 and the potential for novel zoonosis of primate lentiviruses.

microbiology↗

bioRxiv2026

Early immune responses anticipate HIV rebound and precede viral control

Sustained viral suppression following antiretroviral treatment (ART) cessation is a major goal of HIV cure research1. Rare individuals mount immune responses able to control viral rebound without intervention2,3, however, the earliest moments in which these responses form remain poorly defined. We performed an intensively sampled, prospective analytical treatment interruption (ATI) to study the initial immune response to rebound and to understand its role in defining subsequent virus control. Profiling of peripheral blood mononuclear cells and plasma revealed consistent immune activation prior to systemic rebound, including upregulation of antiviral transcriptional pathways, expansion of CD16++ non-classical monocytes, and increases of inflammatory and antiviral soluble plasma proteins. Individuals with prior viral control (controllers) diverged from non-controllers with a slower slope of rebound, a longer period of immune activity prior to rebound, and engagement of a multifaceted immune program with less systemic inflammation. An intermediate immune signature emerged in a separate ATI cohort of individuals who experienced delayed rebound after receiving broadly neutralizing antibodies4, suggesting that immunotherapy can induce a potentially protective pre-rebound immune response. Together, these data resolve the earliest systemic host immune responses to HIV rebound and demonstrate broad immune differences associated with HIV control phenotypes.

immunology↗

bioRxiv2025

Monodisperse LNPs - from Efficient Microfluidic Production and Loading to in Vitro Testing

Carrier nanoparticles facilitate the encapsulation of drug or mRNA molecules thereby enhancing their bioavailability. Microfluidic mixers provide a unique environment for the precise and continuous generation of nanoparticles by antisolvent precipitation. A major challenge is to understand the influence of microfluidic channel designs and geometries on the continuous production of small, uniform lipid nanoparticles (LNPs) and to identify conditions that ensure effective and controllable mixing of aqueous and organic phases in laminar flows. Another important challenge is that sufficient quantities for preclinical and clinical studies must be produced within a reasonable period of time. With this dual objective, different versions of a low aspect ratio laminar mixer (LARLM) were produced using two-photon polymerization (2PP). In the LARLM the organic phase forms a thin layer a few micrometers with a uniform velocity distribution in the center of the channel, surrounded by the aqueous phase. This concept has three major advantages: Firstly, it keeps all particles centralized in the channel, thus preventing contamination during prolonged particle generation. Secondly, diffusive mixing in the thin central stream occurs very quickly, and thirdly, the growing nanoparticles move at a homogeneous speed, which enables inline measurement of the particles. In systematic experiments with design versions of varied channel dimensions the operational parameters such as lipid concentrations and flow rates and the capability to produce LNPs with desired properties and loading capacities were explored. An interfacial dispersion model (IDM) could explain the surprising reduction of particle sizes with increased productivity. The latter allowed us to produce nanoparticles in the range of 50 nm to 180 nm (with 0.02 < PDI < 0.1) under stable conditions with a productivity of around one liter of LNP suspensions every three hours. Such performance has never been reached before with microfluidics. Moreover, LNPs loaded with coumarine-6 and various drugs were produced in the LARLM. Moreover, in-vitro experiments could confirm an improved bioavailability of coumarin-6 in cell culture experiments when loaded in LNPs by the LARLM. These results highlight the unique capabilities of LARLM devices and their potential to support nanoparticle formulation studies including preclinical and in further developments also clinical studies as required for approval as a marketable medicine.

bioengineering↗