A Possible Case of Varicella Zoster Virus (VZV) Meningoencephalitis in an Immunocompetent Host.

The herpes zoster infection occurs in the United States, particularly targeting those who are immunocompromised, and can present with many manifestations including encephalitis. Instances of varicella zoster virus (VZV) encephalitis in immunocompetent patients have been rarely reported, but such diagnoses are becoming more frequent as detection of VZV has improved with the adoption of molecular diagnostic panels such as the BioFire Film Array meningitis panel (Salt Lake City, USA). Here, we present an interesting case of acute meningoencephalitis in an immunocompetent adult female without dermatomal neuralgia or cutaneous lesions attributable to VZV. Given many inconsistencies between the patient's presentation and the positive polymerase chain reaction (PCR) result for VZV, we suspected our patient was infected with an undetected organism while possibly simultaneously shedding previously acquired VZV. As molecular diagnostic panels are increasingly used and have greatly improved detection of rarer etiologies of disease, we encourage clinicians to interpret results with caution.

A rare case of a novel coagulase negative Staphylococcus native valve endocarditis in a 28-year-old male.

Coagulase negative staphylococci (CoNS) are an emerging cause of native valve endocarditis in community and healthcare settings. We describe a case of a 28-year-old man with no significant risk factors who presented with Staphylococcus pettenkoferi native valve endocarditis. During our patient's initial hospitalization, he was treated for CoNS bacteraemia and subsequently discharged after a protracted hospital course with a transthoracic echocardiogram (TTE) showing no valvular vegetations. However, during the course of his second hospitalization, speciation identified S. pettenkoferi and transoesophageal echocardiogram (TEE) showed aortic valve perforations with new regurgitation raising concern for left sided endocarditis. We postulate that our patient may have been infected with the same CoNS species causing aortic valve endocarditis during his initial hospitalization. This case highlights the importance of recognizing CoNS as a possible causative bacterium in NVE, as well as the importance of obtaining a TEE when evaluating a patient for suspected endocarditis.

APOL1 risk variants and the development of HIV-associated nephropathy.

HIV-associated nephropathy (HIVAN) remains a concern among untreated HIV patients, notably of African descent, as patients can reach end-stage renal disease within 3 years. Two variants (G1 and G2) of the APOL1 gene, common in African populations to protect against African sleeping sickness, have been associated with an increased risk of several glomerular disorders including HIVAN, hypertension-attributed chronic kidney disease, and idiopathic focal segmental glomerulosclerosis and are accordingly named renal risk variants (RRVs). This review examines the mechanisms by which APOL1 RRVs drive glomerular injury in the setting of HIV infection and their potential application to patient management. Innate antiviral mechanisms activated by chronic HIV infection, especially those involving type 1 interferons, are of particular interest as they have been shown to upregulate APOL1 expression. Additionally, the downregulation of miRNA 193a (a repressor of APOL1) is also associated with the upregulation of APOL1. Interestingly, glomerular damage affected by APOL1 RRVs is caused by both loss- and gain-of-function changes in the protein, explicitly characterizing these effects. Their intracellular localization offers a further understanding of the nuances of APOL1 variant effects in promoting renal disease. Finally, although APOL1 variants have been recognized as a critical genetic player in mediating kidney disease, there are significant gaps in their application to patient management for screening, diagnosis, and treatment.

HIV-induced kidney cell injury: role of ROS-induced downregulated vitamin D receptor.

Reactive oxygen species (ROS) have been demonstrated to contribute to HIV-induced tubular cell injury. We hypothesized that HIV-induced ROS generation may be causing tubular cell injury through downregulation of vitamin D receptor (VDR) and associated downstream effects. In the present study, HIV not only downregulated tubular cell VDR expression but also inflicted DNA injury. On the other hand, EB-1089, a VDR agonist (VD), inhibited both downregulation of VDR and tubular cell DNA injury in the HIV milieu. H(2)O(2) (an O(-) donor) directly downregulated tubular cell VDR, whereas catalase, a free radical scavenger, inhibited HIV-induced downregulation of tubular cell VDR expression. HIV also stimulated the tubular cell renin-angiotensin system (RAS) through downregulation of VDR. Because losartan (an ANG II blolcker) partially inhibited HIV-induced tubular cell ROS generation while ANG II directly stimulated tubular cell ROS generation, it appears that HIV-induced ROS production was partly contributed by the RAS activation. VD not only inhibited HIV-induced RAS activation but also attenuated tubular cell ROS generation. Tubular cells displayed double jeopardy in the HIV milieu induction of double-strand breaks and attenuated DNA repair; additionally, in the HIV milieu, tubular cells exhibited enhanced expression of phospho-p53 and associated downstream signaling. A VDR agonist and an ANG II blocker not only preserved expression of tubular cell DNA repair proteins but also inhibited induction of double-strand breaks. In in vivo studies, renal cortical sections of Tg26 mice displayed attenuated expression of VDR both in podocytes and tubular cells. In addition, renal cortical sections of Tg26 mice displayed enhanced oxidative stress-induced kidney cell DNA damage. These findings indicated that HIV-induced tubular cell downregulation of VDR contributed to the RAS activation and associated tubular cell DNA damage. However, both VD and RAS blockade provided protection against these effects of HIV.