HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.

Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood and a model for mechanisms of viral replication, immune evasion and pathogenesis. In this review, we consider the earliest stages of HIV infection from transport of the virion contents through the cytoplasm to integration of the viral genome into host chromatin. We present a holistic model for the virus-host interaction during this pivotal stage of infection.

Delocalized quinolinium-macrocyclic peptides, an atypical chemotype for CNS penetration.

Macrocyclic drugs can address an increasing range of molecular targets but enabling central nervous system (CNS) access to these drugs has been viewed as an intractable problem. We designed and synthesized a series of quinolinium-modified cyclosporine derivatives targeted to the mitochondrial cyclophilin D protein. Modification of the cation to enable greater delocalization was confirmed by x-ray crystallography of the cations.

HIV-1 with gag processing defects activates cGAS sensing.

Background: Detection of viruses by host pattern recognition receptors induces the expression of type I interferon (IFN) and IFN-stimulated genes (ISGs), which suppress viral replication. Numerous studies have described HIV-1 as a poor activator of innate immunity in vitro. The exact role that the viral capsid plays in this immune evasion is not fully understood.

Vaginal Calculus Formation on Exposed Midurethral Sling Mesh.

The presence of a vaginal calculus is a rare clinical entity which may develop in the setting of vaginal urinary stagnation. Numerous factors contribute to stone formation, and management can be complicated by variations in size, location of the stone, and location of adjacent structures. Generally, once diagnosed, vaginal calculi should be removed and surrounding anatomy should be evaluated thoroughly for secondary fistula, erosion, or presence of an instituting foreign body.