The Great Escape: Viral Strategies to Counter BST-2/Tetherin

The interferon-induced BST-2 protein has the unique ability to restrict the egress of HIV-1, Kaposi's sarcoma–associated herpesvirus (KSHV), Ebola virus, and other enveloped viruses. The observation that virions remain attached to the surface of BST-2-expressing cells led to the renaming of BST-2 as “tetherin”. However, viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells. Since the anti-viral function of BST-2 was discovered, there has been an explosion of research into several aspects of this intriguing interplay between host and virus. This review focuses on recent work addressing the molecular mechanisms involved in BST-2 restriction of viral egress and the species-specific countermeasures employed by various viruses

Prevalence of Occult Hepatitis B in HIV Positive Patients (Adolescents and Adults) in Kermanshah- Iran

Background Occult hepatitis B infection (OBI) is considered a risk factor for progression of liver disease in patients with hepatitis B virus (HBV) infection. This disease progression is reported to be more significant in those with concomitant HIV infection. We aimed to determine the prevalence rate of OBI in a sample of HIV-positive patients. Materials and Methods: Sixty-six HIV-infected patients with positive Hepatitis B core antigen (HBcAb) and negative Hepatitis B surface antigen HBsAg were included. HBV DNA was measured by real time polymerase chain reaction PCR method. Those with positive HBV viral load were considered as seropositive OBI. Then, the patients were studied regarding age, gender, intravenous drug use (IVDU), CD4 count, and concomitant infection by hepatitis C virus (HCV), available in their medical records. Results: Seventy-seven patients (38.5%) had positive HBc antibody (HBcAb). Of 66 patients who were positive for both HIV and HBc antibody, eight patients (12.12%) had OBI. About 3.7% in age group younger than 40 years and 5.3% in age group older than 40 years, OBI was detected. Forty-four patients (54.5%) were male. OBI rate was 22.2% in males and zero in females (P 350/mL, 4.1% had OBI. In those who were IV drug user, 17.94% and in those who were not IV drug user, 3.57% gad OBI. Conclusion The prevalence of OBI in the studied sample of HIV-infected patients is considerable. As we did not find any significant association between OBI and studied factors except for gender, we think that screening for OBI would be useful for HIV-infected patients, especially male patients

BST2/Tetherin Enhances Entry of Human Cytomegalovirus

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV

Membrane-Associated RING-CH Proteins Associate with Bap31 and Target CD81 and CD44 to Lysosomes

Membrane-associated RING-CH (MARCH) proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover of transmembrane protein targets. While homologous proteins encoded by gamma-2 herpesviruses and leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets of cellular MARCH proteins. To identify host cell proteins targeted by the human MARCH-VIII ubiquitin ligase we used stable isotope labeling of amino-acids in cell culture (SILAC) to monitor MARCH-dependent changes in the membrane proteomes of human fibroblasts. Unexpectedly, we observed that MARCH-VIII reduced the surface expression of Bap31, a chaperone that predominantly resides in the endoplasmic reticulum (ER). We demonstrate that Bap31 associates with the transmembrane domains of several MARCH proteins and controls intracellular transport of MARCH proteins. In addition, we observed that MARCH-VIII reduced the surface expression of the hyaluronic acid-receptor CD44 and both MARCH-VIII and MARCH-IV sequestered the tetraspanin CD81 in endo-lysosomal vesicles. Moreover, gene knockdown of MARCH-IV increased surface levels of endogenous CD81 suggesting a constitutive involvement of this family of ubiquitin ligases in the turnover of tetraspanins. Our data thus suggest a role of MARCH-VIII and MARCH-IV in the regulated turnover of CD81 and CD44, two ubiquitously expressed, multifunctional proteins

Variant-specific surface protein (VSP) gene subsets in Giardia / by Mandana Mansouri.

Includes bibliographical references (leaves 117-133).v, 133 leaves, 5 leaves of photographic plates : ill. (some col.); 30 cm.Concerned with the family of genes that encode variant-specific surface proteins in the parasitic protzoon, Giardia. Specific goals were to identify and compare closely related genes, which may form subsets within the larger VSP gene family.Thesis (Ph.D.)--Adelaide University, Dept. of Molecular Biosciences, 200

Remodeling of Endothelial Adherens Junctions by Kaposi's Sarcoma-Associated Herpesvirus▿

Vascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits α- and β-catenins and γ-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of α- and β-catenins and γ-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis

Septic arthritis of both knees following intra-articulari njection of petrol

Abstract: A 70 years old man was referred to our center with bilateral knee arthritis following intra-articular petrol injection. Because of previous antibiotics use gram stain and culture were negative. Septic arthritis was diagnosed and antibiotics and drainage were started. After 2 years he improved eventually and was able to walk. But, some movement limitation remained

Downregulation of Major Histocompatibility Complex Class I by Human Ubiquitin Ligases Related to Viral Immune Evasion Proteins

Poxviruses and gamma-2 herpesviruses share the K3 family of viral immune evasion proteins that inhibit the surface expression of glycoproteins such as major histocompatibility complex class I (MHC-I), B7.2, ICAM-1, and CD95(Fas). K3 family proteins contain an amino-terminal PHD/LAP or RING-CH domain followed by two transmembrane domains. To examine whether human homologues are functionally related to the viral immunoevasins, we studied seven membrane-associated RING-CH (MARCH) proteins. All MARCH proteins located to subcellular membranes, and several MARCH proteins reduced surface levels of known substrates of the viral K3 family. Two closely related proteins, MARCH-IV and MARCH-IX, reduced surface expression of MHC-I molecules. In the presence of MARCH-IV or MARCH-IX, MHC-I was ubiquitinated and rapidly internalized by endocytosis, whereas MHC-I molecules lacking lysines in their cytoplasmic tail were resistant to downregulation. The amino-terminal regions containing the RING-CH domain of several MARCH proteins examined catalyzed multiubiquitin formation in vitro, suggesting that MARCH proteins are ubiquitin ligases. The functional similarity of the MARCH family and the K3 family suggests that the viral immune evasion proteins were derived from MARCH proteins, a novel family of transmembrane ubiquitin ligases that seems to target glycoproteins for lysosomal destruction via ubiquitination of the cytoplasmic tail

Effect of Propolis on Dentin Regeneration and the Potential Role of Dental Pulp Stem Cell in Guinea Pigs

Objective: Evaluation of the effect of Propolis as a bioactive material on quality of dentinand presence of dental pulp stem cells.Materials and Methods: For conducting this experimental split-mouth study,a total of48 maxillary and mandibular incisors of male guinea pigs were randomly divided into anexperimental Propolis group and a control calcium hydroxide group. Cutting the crownsand using Propolis or calcium hydroxide to cap the pulp, all of the cavities were sealed.Sections of the teeth were obtained after sacrificing 4 guinea pigs from each group on the10th, 15th and 30th day. After they had been stained by hematoxylin and eosin (H&E),specimens underwent a histological evaluation under a light microscope for identificationof the presence of odontoblast-like cells, pulp vitality, congestion, inflammation of the pulpand the presence of remnants of the material used. The immunohistochemistry (IHC)method using CD29 and CD146 was performed to evaluate the presence of stem cells andthe results were statistically evaluated by Kruskal-Wallis, Chi Square and Fisher tests.Results: In H&E stained specimens, there was no difference between the two groups inthe presence of odontoblast-like cells, pulp vitality, congestion, inflammation of the pulpand the presence of remnants of used material(p>0.05). There was a significant differencebetween the quality of regenerative dentin on the 15th and 30th days (p<0.05): all of thePropolis cases presented tubular dentin while 14% of the calcium hydroxide cases producedporous dentin. There was no significant difference between Propolis and calciumhydroxide in stimulation of dental pulp stem cells (DPSCs).Conclusion: This study which is the first one that documented the stimulation of stem cellsby Propolis, provides evidence that this material has advantages over calcium hydroxideas a capping agent in vital pulp therapy. In addition to producing no pulpal inflammation,infection or necrosis this material induces the production of high quality tubular dentin