Detection and characterization of HIV type 2 in Calcutta, India

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.     

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

The loss of Gimap5 (GTPase of the immune-associated protein 5) gene function is the underlying cause of lymphopenia and autoimmune diabetes in the BioBreeding (BB) rat. The in vivo function of murine gimap5 is largely unknown. We show that selective gene ablation of the mouse gimap5 gene impairs the final intrathymic maturation of CD8 and CD4 T cells and compromises the survival of postthymic CD4 and CD8 cells, replicating findings in the BB rat model. In addition, gimap5 deficiency imposes a block of natural killer (NK)- and NKT-cell differentiation. Development of NK/NKT cells is restored on transfer of gimap5(-/-) bone marrow into a wild-type environment. Mice lacking gimap5 have a median survival of 15 weeks, exhibit chronic hepatic hematopoiesis, and in later stages show pronounced hepatocyte apoptosis, leading to liver failure. This pathology persists in a Rag2-deficient background in the absence of mature B, T, or NK cells and cannot be adoptively transferred by transplanting gimap5(-/-) bone marrow into wild-type recipients. We conclude that mouse gimap5 is necessary for the survival of peripheral T cells, NK/NKT-cell development, and the maintenance of normal liver function. These functions involve cell-intrinsic as well as cell-extrinsic mechanisms.     

Prevalence and Comorbidity of Insomnia and Effect on Functioning in Elderly Populations

A good night's sleep is often more elusive as we age, because the prevalence of insomnia in older people is high. Insufficient sleep can have important effects on daytime function by increasing the need to nap, reducing cognitive ability including attention and memory, slowing response time, adversely affecting relationships with friends and family, and contributing to a general sense of being unwell. However, rather than aging per se, circadian rhythm shifts, primary sleep disorders, comorbid medical/psychiatric illnesses, and medication use cause sleep difficulties in older people, which psychosocial factors may also affect. Clinicians should ask elderly patients about satisfaction with sleep. Any sleep complaints warrant careful evaluation of contributing factors and appropriate treatment.     

Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity

Protein aggregation and ordered fibrillar amyloid deposition inside and outside of the central nervous system cells is the common pathologic hallmark of most aging-related neurodegenerative disorders. Dominant mutations in the gene encoding superoxide dismutase 1 (SOD1) protein are linked to familial amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive degeneration of motor neurons, leading to muscle paralysis and death. The major histochemical hallmark in the remaining motor neurons of ALS is the intracellular accumulation of ubiquitinated inclusions consisting of insoluble aberrant protein aggregates. However, the molecular pathomechanisms underlying the process have been elusive. Here for the first time, we report that E6-AP, a homologous to E6-AP C terminus-type E3 ubiquitin ligase depleted in ALS mouse models before neurodegeneration. E6-AP coimmunoprecipitates with the SOD1 protein and is predominantly mislocalized in mutant SOD1-containing inclusion bodies. Overexpression of E6-AP increases the ubiquitination and facilitates degradation of SOD1 proteins. Finally, we show that the overexpression of E6-AP suppresses the aggregation and cell death mediated by mutated SOD1 proteins and cellular protective effect is more prominent when E6-AP is overexpressed along with Hsp70. These data suggest that enhancing the activity of E6-AP ubiquitin ligase might be a viable therapeutic strategy to eliminate mutant SOD1-mediated toxicity in ALS.     

Genetic diversity of porcine sapoviruses, kobuviruses, and astroviruses in asymptomatic pigs: an emerging new sapovirus GIII genotype

Small, non-enveloped RNA viruses belonging to the genera Sapovirus, Kobuvirus, and Mamastrovirus are usually associated with gastroenteritis in humans and animals. These enteric pathogens are considered potential zoonotic agents. In this study, the prevalence and genetic diversity of sapoviruses (SaVs), kobuviruses (KoVs), and astroviruses (AstVs) in asymptomatic pigs were investigated using a PCR approach. KoV was found to be the most prevalent virus (87.3 %), followed by AstV (34.2 %) and SaV (10.2 %). Interestingly, the intra- and inter-cluster distances between porcine SaV capsid sequences revealed one strain (P38/11/CZ) that formed a new genotype within genogroup III of porcine SaVs, and it is tentatively called “P38/11-like” genotype. Moreover, this is the first report of porcine kobuvirus detection on Czech pig farms. The high prevalence rate of gastroenteritis-producing viruses in clinically healthy pigs represents a continuous source of infection of pigs, and possibly to humans.     

Small body size of pseudoscorpions and a distinct architecture of the ovary: A step to miniaturization?

Chelicerata, the second largest subphylum of Arthropoda, includes invertebrates with a wide range of body size. Pseudoscorpions are among small or miniature chelicerates which exhibit several morphological, anatomical, and developmental features related to miniaturization, e.g., replacement of book lungs by tracheae, unpaired gonads, and matrotrophic development of the embryos outside the female body, in the brood sac. In this paper, we show the ovary structure of two pseudoscorpion species, Cheiridium museorum and Apocheiridium ferum (Cheiridiidae). Both cheiridiids are one of the smallest pseudoscorpions. The results of our observations conducted in light, transmission electron, and confocal microscopy demonstrate that the ovary of C. museorum and A. ferum, displays a significant structural difference that is unusual for chelicerates. The difference concerns the spatially restricted position of the germarium. We show that such ovary architecture results in a significantly reduced number of growing oocytes and in consequence a reduced number of deposited eggs. A centrally located germarium implies also a modified pattern of ovary development during oocyte growth due to long distance migration of the germline and the accompanying somatic cells. Herein, we postulate that such an ovary structure is related to the pseudoscorpion's small body size and it is a step towards miniaturization in the smaller pseudoscorpions species.     

Eczema herpeticum in atopic dermatitis

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases leading to pruritic skin lesions. A subset of AD patients exhibits a disseminated severe HSV infection called eczema herpeticum (EH) that can cause life-threatening complications. This review gives an overview of the clinical picture, and characteristics of the patients as well as the diagnosis and therapy of EH. A special focus lies on the pathophysiological hallmarks identified so far that predispose for EH. This aspect covers genetic aberrations, immunological changes, and environmental influences displaying a complex multifactorial situation, which is not completely understood. Type 2 skewing of virus-specific T cells in ADEH⁺ patients has been implicated in immune profile abnormalities, along with impaired functions of dendritic cells and natural killer cells. Furthermore, aberrations in interferon pathway-related genes such as IFNG and IFNGR1 have been identified to increase the risk of EH. IL-4, IL-25, and thymic stromal lymphopoietin (TSLP) are overexpressed in EH, whereas antimicrobial peptides like human β-defensins and LL-37 are reduced. Concerning the epidermal barrier, single nucleotide polymorphisms (SNPs) in skin barrier proteins such as filaggrin were identified in ADEH⁺ patients. A dysbalance of the skin microbiome also contributes to EH due to an increase of Staphylococcus aureus, which provides a supporting role to the viral infection via secreted toxins such as α-toxin. The risk of EH is reduced in AD patients treated with dupilumab. Further research is needed to identify and specifically target risk factors for EH in AD patients.