Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways.

Cancer is a multifactorial disease and virus-mediated carcinogenesis is one of the crucial factors, which is poorly understood. Human cytomegalovirus (HCMV) is a herpesvirus and its components have been evidenced to be associated with cancer of different tissue origin. However, its role in cancer remains unknown.

Herpesviruses: interfering innate immunity by targeting viral sensing and interferon pathways.

Type I-interferon (IFN-I) induction pathway is one of the most commonly stimulated signaling pathways in response to viral infection. During viral infection this pathway is stimulated by various pattern-recognition receptors, which recognize different pathogen-associated molecular patterns. The pathways stimulated by different pattern-recognition receptors merge into common transcription factors IRF3 and IRF7, lead to the production of IFN-I.

Tegument Proteins of Kaposi's Sarcoma-Associated Herpesvirus and Related Gamma-Herpesviruses.

A herpesvirus virion is composed of a viral genomic DNA-containing capsid surrounded by a viral envelope with glycoprotein spikes on its surface. Located between the capsid and the outer viral envelope is the virion tegument layer. Though the majority of the virion proteins are located in the tegument, this layer is less studied and was thought to be an amorphous structure.

Multifunctional Ebselen drug functions through the activation of DNA damage response and alterations in nuclear proteins.

Several studies have demonstrated that Ebselen is an anti-inflammatory and anti-oxidative agent. Contrary to this, studies have also shown a high degree of cellular toxicity associated with Ebselen usage, the underlying mechanism of which remains less understood. In this study we have attempted to identify a possible molecular mechanism behind the above by investigating the effects of Ebselen on Saccharomyces cerevisiae.

Evasion and subversion of interferon-mediated antiviral immunity by Kaposi's sarcoma-associated herpesvirus: an overview.

Viral invasion of a host cell triggers immune responses with both innate and adaptive components. The innate immune response involving the induction of type I interferons (alpha and beta interferons [IFN-α and -β]) constitutes the first line of antiviral defenses. The type I IFNs signal the transcription of a group of antiviral effector proteins, the IFN-stimulated genes (ISGs), which target distinct viral components and distinct stages of the viral life cycle, aiming to eliminate invading viruses.

Functional characterization of Kaposi's sarcoma-associated herpesvirus open reading frame K8 by bacterial artificial chromosome-based mutagenesis.

The open reading frame K8 of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a basic leucine zipper (bZip) protein that binds to the origin of viral DNA replication and is an integral component of viral lytic DNA replication complex. Moreover, K8 physically interacts with replication and transcription activator (RTA) and represses its transactivation activity on several viral promoters. To investigate the role of this protein in viral life cycle, we constructed two K8-null recombinant mutant viruses (BAC-ΔK8 and BAC-stopK8) by using a bacterial artificial chromosome (BAC) system.

Mechanisms of autoinhibition of IRF-7 and a probable model for inactivation of IRF-7 by Kaposi's sarcoma-associated herpesvirus protein ORF45.

IRF-7 is the master regulator of type I interferon-dependent immune responses controlling both innate and adaptive immunity. Given the significance of IRF-7 in the induction of immune responses, many viruses have developed strategies to inhibit its activity to evade or antagonize host antiviral responses. We previously demonstrated that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu, F.

Functional characterization of Kaposi's sarcoma-associated herpesvirus small capsid protein by bacterial artificial chromosome-based mutagenesis.

A systematic investigation of interactions amongst KSHV capsid proteins was undertaken in this study to comprehend lesser known KSHV capsid assembly mechanisms. Interestingly the interaction patterns of the KSHV small capsid protein, ORF65 suggested its plausible role in viral capsid assembly pathways. Towards further understanding this, ORF65-null recombinant mutants (BAC-∆65 and BAC-stop65) employing a bacterial artificial chromosome (BAC) system were generated.

Antagonism of host antiviral responses by Kaposi's sarcoma-associated herpesvirus tegument protein ORF45.

Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV) is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection.

Can recurrence of cervical cancer be predicted by human papillomavirus DNA in nodes or plasma?

Objective: To determine if human papillomavirus (HPV) DNA in pelvic lymph nodes or plasma of women with early-stage cervical cancer is a marker for recurrence.

Materials And Methods: Twenty-eight women undergoing radical hysterectomy for cervical cancer stage IB had HPV DNA testing in cervical tissue, plasma, and the largest lymph nodes. Human papillomavirus genotyping was done by restriction fragment length polymorphism/line blot assay.

Kaposi's sarcoma-associated herpesvirus ORF45 interacts with kinesin-2 transporting viral capsid-tegument complexes along microtubules.

Open reading frame (ORF) 45 of Kaposi's sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen.

Virion-wide protein interactions of Kaposi's sarcoma-associated herpesvirus.

Herpesvirus virions are highly organized structures built through specific protein-protein interactions. Thus, revelation of the protein interactions among virion proteins will shed light on the processes and the mechanisms of virion formation. Recently, we identified 24 virion proteins of Kaposi's sarcoma-associated herpesvirus (KSHV), using a proteomic approach (F.

HPV 16 E6 sequence variations in Indian patients with cervical neoplasia.

In a cross-sectional study performed between June 2001 and November 2003, the HPV 16 E6 gene of 50 women with cervical neoplasia and 20 cytologically normal women ('controls') was sequenced following amplification by PCR. The 350T to G variant was seen in 35 (70%) of 50 patients' isolates while it was seen in only 3 (15%) of the 20 isolates from the 'controls'. The higher occurrence of the 350G variant among the patients was statistically significant (P<0.

Is dengue emerging as a major public health problem?

Background & Objectives: Diagnosis of dengue infection is easily and best accomplished by demonstration of specific IgM antibodies in blood. We analyzed retrospectively the dengue IgM seropositivity available for samples obtained over a period of five year (1999-2003) from patients with suspected dengue fever (DF)-like illness to investigate whether there was an overall increase in the dengue IgM prevalence over this period.

Methods: Serum samples from a total of 1426 individuals (suspected dengue cases) obtained over five year were tested for dengue specific IgM antibodies.

E2 sequence variations of HPV 16 among patients with cervical neoplasia seen in the Indian subcontinent.

Objectives: Specific nucleotide variations in the E2 DNA sequence were looked for in samples with an intact human papillomavirus (HPV) 16 episomal E2 DNA.

Methods: Ninety-two women, 76 with invasive cervical carcinoma and 16 with cervical intraepithelial neoplasia (CIN) were recruited. HPV DNA typing was performed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP).

HPV DNA in plasma of patients with cervical carcinoma.

Background: HPV DNA has been detected in metastatic tumour and HPV plasma viraemia may indicate a poor prognosis and a high risk for metastasis.

Objective: Detection of HPV DNA in plasma of patients with cervical carcinoma.

Study Design: A cross-sectional study was done, wherein cervical biopsies and plasma samples were collected from 58 women with invasive cervical carcinoma, 10 women with cervical intraepithelial neoplasia (CIN) and 30 control women in the same age range.

Human papillomavirus 16 E6/E7 transcript and E2 gene status in patients with cervical neoplasia.

Background: The viral transforming genes E6 and E7 of human papillomavirus (HPV) 16 cause the degradation of tumor suppressor proteins. Expression of these oncoproteins increases following the integration of viral DNA into the host cell, resulting in the disruption of the E2 open reading frame (ORF).

Aim: To detect and correlate HPV-16 oncogene transcripts and HPV-16 E2 DNA in cervical biopsies obtained from women (n = 68) with cervical neoplasia.

An outbreak of echovirus meningitis in children.

An outbreak of aseptic meningitis in children as evidenced by increase in the number of admissions in a tertiary care hospital is described. Clinical data and stool samples were collected from 25 hospitalized infants and young children. The stool samples were subjected to virological investigations.