Herpesvirus-associated ubiquitin-specific protease (HAUSP) is a USP family deubiquitinase. HAUSP is a protein of immense biological importance as it is involved in several cellular processes, including host-virus interactions, oncogenesis and tumor suppression, DNA damage and repair processes, DNA dynamics and epigenetic modulations, regulation of gene expression and protein function, spatio-temporal distribution, and immune functions. Since its discovery in the late 1990s as a protein interacting with a herpes virus regulatory protein, extensive studies have assessed its complex roles in p53-MDM2-related networks, identified numerous additional interacting partners, and elucidated the different roles of HAUSP in the context of cancer, development, and metabolic and neurological pathologies. Recent analyses have provided new insights into its biochemical and functional dynamics. In this review, we provide a comprehensive account of our current knowledge about emerging insights into HAUSP in physiology and diseases, which shed light on fundamental biological questions and promise to provide a potential target for therapeutic intervention.

The positive sense genomes of members of the genus Flavivirus in the family Flaviviridae are ~11 kb nts in length and have a 5′ type I cap but no 3′ poly A. The 5′ and 3′ terminal regions contain short conserved sequences that are proposed to be repeated remnants of an ancient sequence. However, the functions of most of these conserved sequences have not yet been determined. The terminal regions of the genome also contain multiple conserved RNA structures. Functional data for many of these structures has been obtained. Three sets of complementary 3′ and 5′ terminal region sequences, some of which are located in conserved RNA structures, interact to form a panhandle structure that is required for initiation of minus strand RNA synthesis with the 5′ terminal structure functioning as the promoter. How the switch from the terminal RNA structure base pairing to the long distance RNA-RNA interaction is triggered and regulated is not well understood but evidence suggests involvement of a cell protein binding to three sites on the 3′ terminal RNA structures and a cis-acting metastable 3′ RNA element in the 3′ terminal structure. Cell proteins may also be involved in facilitating exponential replication of nascent genomic RNA within replication vesicles at later times of infection cycle. Other conserved RNA structures and/or sequences in the 5′ and 3′ terminal regions have been proposed to regulate genome translation. Additional functions of the 5′ and 3′ terminal sequences have also been reported.

Human parainfluenza virus type 3 (HPIV-3) is an airborne pathogen that infects human lung epithelial cells from the apical (luminal) plasma membrane domain. In the present study, we have identified cell surfaceexpressed nucleolin as a cellular cofactor required for the efficient cellular entry of HPIV-3 into human lung epithelial A549 cells. Nucleolin was enriched on the apical cell surface domain of A549 cells, and HPIV-3 interacted with nucleolin during entry. The importance of nucleolin during HPIV-3 replication was borne out by the observation that HPIV-3 replication was significantly inhibited following (i) pretreatment of cells with antinucleolin antibodies and (ii) preincubation of HPIV-3 with purified nucleolin prior to its addition to the cells. Moreover, HPIV-3 cellular internalization and attachment assays performed in the presence of antinucleolin antibodies and purified nucleolin revealed the requirement of nucleolin during HPIV-3 internalization but not during attachment. Thus, these results suggest that nucleolin expressed on the surfaces of human lung epithelial A549 cells plays an important role during HPIV-3 cellular entry.

Oxidative stress activates the cellular kinase HRI, which then phosphorylates eIF2α, resulting in stalled translation initiation and the formation of stress granules (SGs). SG assembly redirects cellular translation to stress response mRNAs and inhibits cap-dependent viral RNA translation. Flavivirus infections were previously reported to induce oxidative stress in infected cells but flavivirus-infected cells paradoxically develop resistance to arsenite (Ars)-induced SG formation with time after infection. This resistance was previously postulated to be due to sequestration of the SG protein Caprin1 by Japanese encephalitis virus capsid protein. However, Caprin1 did not co-localize with West Nile virus (WNV) capsid protein in infected cells. Other stressors induced SGs with equal efficiency in mock- and WNV-infected cells indicating the intrinsic ability of cells to assemble SGs was not disabled. Induction of both reactive oxygen species (ROS) and the antioxidant response was detected at early times after WNV-infection. The transcription factors, Nrf2 and ATF4, which activate antioxidant genes, were upregulated and translocated to the nucleus. Knockdown of Nrf2, ATF4 or apoptosis-inducing factor (AIF), a mitochondrial protein involved in regenerating intracellular reduced glutathione (GSH) levels, with siRNA or treatment of cells with buthionine sulphoximine, which induces oxidative stress by inhibiting GSH synthesis, decreased intracellular GSH levels and increased the number of SG-positive, infected cells. Mitochondria were protected from Ars-induced damage by WNV infection until late times in the infection cycle. The results indicate that the increase in virus-induced ROS levels is counterbalanced by a virus-induced antioxidant response that is sufficient to also overcome the increase in ROS induced by Ars treatment and prevent Ars-induced SG assembly and mitochondrial damage. The virus-induced alterations in the cellular redox status appear to provide benefits for the virus during its lifecycle.

The 3=-terminal nucleotides (nt) of West Nile virus (WNV) genomic RNA form a penultimate 16-nt small stem-loop (SSL) and an 80-nt terminal stem-loop (SL). These RNA structures are conserved in divergent flavivirus genomes. A previous in vitro study using truncated WNV 3= RNA structures predicted a putative tertiary interaction between the 5= side of the 3=-terminal SL and the loop of the SSL. Although substitution or deletion of the 3= G (nt 87) within the SSL loop, which forms the only G-C pair in the predicted tertiary interaction, in a WNV infectious clone was lethal, a finding consistent with the involvement in a functionally relevant pseudoknot interaction, extensive mutagenesis of nucleotides in the terminal SL did not identify a cis-acting pairing partner for this SSL 3= G. However, both the sequence and the structural context of two adjacent base pairs flanked by symmetrical internal loops in the 3=-terminal SL were shown to be required for efficient viral RNA replication. Nuclear magnetic resonance analysis confirmed the predicted SSL and SL structures but not the tertiary interaction. The SSL was previously reported to contain one of three eEF1A binding sites, and G87 in the SSL loop was shown to be involved in eEF1A binding. The nucleotides at the bottom part of the 3=-terminal SL switch between 3= RNA-RNA and 3=-5= RNA-RNA interactions. The data suggest that interaction of the 3= SL RNA with eEF1A at three sites and a unique metastable structural feature may participate in regulating structural changes in the 3=-terminal SL. West Nile virus (WNV) is a member of the family Flaviviridae, genus flavivirus, and the Japanese encephalitis serogroup. WNV is endemic in Southeastern Asia, Africa, and recently in the Americas. WNV is maintained in a mosquito-bird-mosquito cycle in nature. Mammals, including humans, are incidental "deadend" hosts. WNV infections of humans are usually asymptomatic, but in a few individuals infection results in severe central nervous system diseases that can be fatal (1, 2).The single-stranded, positive sense WNV genomic RNA is ϳ11,000 nucleotides (nt) in length and contains a single open reading frame that encodes a polyprotein that is cleaved by host and viral proteases into three mature structural and seven nonstructural viral proteins. The open reading frame is flanked by a 96-nt 5= noncoding region and an ϳ600-nt 3= noncoding region. Both 3=-and 5=-terminal RNA structures are conserved among divergent flaviviruses (3-5), and the negative effect of their deletion/mutation in infectious clones indicated that these regions contain cis-acting elements (6-12). The 3=-terminal 96 nt of the WNV genomic RNA are predicted to form two stem-loop (SL) structures, a short SL (SSL) followed by a longer terminal SL (see Fig. 1, left-hand panel), and this region is predicted to contain promoter elements important for the synthesis of the viral minus strand RNA. The WNV SSL consists of a 5-bp stem and a 6-nt loop. The majority of the nucleotides of this loop are conserved among divergent mos...

These results indicate that although some strains of H. pylori are capable of survival within the macrophage phagosome, survival is dependent on virulence factors such as catalase for evasion of innate host defense.

These results indicate that the host is capable of spontaneously eradicating H. pylori from the gastric mucosa when inflammation is elevated beyond the chronic inflammation induced in wild-type mice, and that the gastritis dissipates following bacterial eradication. Additionally, these data provide support for a model of gastrointestinal immunity in which naturally occurring IL-10-producing regulatory T cells modulate the host response to gastrointestinal bacteria.

Background: Services are being provided by health functionaries to the community with the objective of fulfilling their satisfaction but sometimes this is not working for the target population.Objectives: The study was conducted to assess the satisfaction of clients′ receiving maternal and child health services and to elicit clients′ suggestion for improving the services.Materials and Methods: Anexit interview was employed to collect data using a predesigned and pretested schedule.Results:Most of the populations were adult clients. In respect of satisfaction, responses of the clients were either satisfactory (54.31%) or good (23.56%) on maternal and child health services; ‘poor or very poor around 20% and it was significantly worse in respect of satisfaction’. Most of the clients (63.06 to 73.94%) expressed their responses as satisfactory and good regarding the assessment of doctors and it was significant. Most of them (73.31%) expressed satisfactory “response” on the quality of services given by nursing staffs. Suggestions of clients for improving the level of satisfactionwere sought and in this respect, response was little.Conclusions:Mostly satisfactory observations on maternal and child health services were found in respect of clients' satisfaction and there was scope to improve the quality and quantity of services, and accordingly actions may be taken in the working field.