Amit Kumar

University Health Network | UHN · Princess Margaret Cancer Centre

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significant...

Background: Human cytomegalovirus (HCMV) establishes a persistent life-long infection and increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. Breast milk is an important route of HCMV transmission in humans and we hypothesized that mammary epithelial cells could be one of the main cellular targ...

We previously reported that the protein-tyrosine phosphatase SHP-1 (PTPN6) negatively regulates insulin signaling, but its impact on hepatic glucose metabolism and systemic glucose control remains poorly understood. Here, we use co-immunoprecipitation assays, chromatin immunoprecipitation sequencing, in silico methods, and gluconeogenesis assay, an...

The protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) plays an important role in modulating glucose and lipid homeostasis. We previously suggested a potential role of SHP-1 in the regulation of peroxisome proliferator-activated receptor γ2 (PPARγ2) expression and activity but the mechanisms were unexplored....

Nuclear transport receptors, termed importins and exportins, regulate protein transport through the nuclear pore. Although genetic alterations in the nuclear pore complex are more common in young AML patients (e.g., NUP98 rearrangements), nucleocytoplasmic transport has not been studied extensively in childhood/young adult AML. We compared the expr...

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications, and chromatin remodelling. Epitranscriptomics is an emerging field that encompasses the study of RNA modifications that do not affect the RNA sequence but affect function...

Effects of glucocorticoids on sirtuin 1 pathway in rheumatoid arthritis R. Bordy1; S. Pasquereau2; W. Abbas2; A. Kumar2; F. Verhoeven1; C. Prati1; D. Wendling3; G. Herbein2; C. Demougeot1; P. Totoson1 1 Pepite EA 4267, FHU Increase, Univ. Bourgogne Franche-Comté, F-25000 - Besançon (France); 2 EA4266 Pathogens & Inflammation/EPILAB Laboratory, Uni...

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed 'epitranscriptomics' has emerged as a new layer of epigenetic regulation due t...

A growing body of evidence addressing the involvement of human cytomegalovirus (HCMV) in malignancies had directed attention to the oncomodulation paradigm. HCMV-DB infected human mammary epithelial cells (HMECs) in culture showed the emergence of clusters of rapidly proliferating, spheroid-shaped transformed cells named CTH (CMV-Transformed HMECs)...

The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions throughout lifespan, including inflammation. A possible association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in endorsing inflammation, articular destruction, and comorbiditi...

Abstract Src homology region 2 domain-containing phosphatase-1 (Shp1) plays an important role in modulating insulin signaling and thereby glucose homeostasis. Our laboratory has demonstrated that despite being more prone to hepatic steatosis, mice with a liver specific Shp1 knock out (Shp1H-KO) on high-fat diet (HFD) exhibit improved fasting glycae...

Increasing evidence indicates that human cytomegalovirus (HCMV) populations under the infuence of host environment, can either be stable or rapidly diferentiating, leading to tissue compartment colonization. We isolated previously from a 30-years old pregnant woman, a clinical isolate of HCMV, that we refered to as the HCMV-DB strain (accession num...

Background Sirtuin 1 (SIRT1) is a class III histone deacetylase which could play a critical role in several biological functions including lifespan, stress, and inflammation. Objectives Our main objective was to evaluate SIRT1 expression in peripheral blood mononuclear cells (PBMCs) isolated from rats with adjuvant induced arthritis (AIA) treated...

Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the i...

Phylogenetic analysis was determined among several HCMV strains including HCMV-DB (described in Table 1) with respect to the UL144 gene as mentioned in Materials and Methods and described previously (Waters et al., 2010).

Sequencing of the 126 bp lncRNA4.9 amplicon detected in CTH cells. The 126 bp lncRNA4.9 amplicon detected in CTH cells was sequenced using Sanger's method and matched with the lncRNA4.9 sequence of HCMV-DB using Blast alignement. Blue boxes represent primers sequences.

The TB40/E strain activates oncogenic pathways in HMECs, but to a lesser extent than the HCMV-DB strain. a. HMECs were infected with HCMV (MOI = 1) and cells were harvested at different time points. Expression of hTERT mRNA was determined by RT-PCR as described in Materials and Methods. b. Increased telomerase activity in HMECs following HCMV infec...

Overexpression of c-Myc (MYC) and cyclin-D1 (CCND1) transcripts in HMECs infected with HCMV-DB as compared to uninfected HMECs using a RT-PCR array assay as described in Materials and Methods. Results are representative of two independent experiments.

Absence of detection of HCMV MIEP DNA in soft agar colonies at day 15 post infection with HCMV-DB (after 14 days of culture in soft agar). DNA was isolated from soft agar HMEC colonies and detection of MIEP and beta-globin (internal control) sequences was performed using PCR. Results are representative of two independent experiments.

The human cytomegalovirus (HCMV) is a betaherpesvirus that is highly host specific, infects among others epithelial cells and macrophages, and has been recently mentioned as having oncomodulatory properties. HCMV is detected in the breast tumor tissue where macrophages, especially tumor associated macrophages, are associated with a poor prognosis....

Several cellular functions such as apoptosis, cellular proliferation, inflammation, and immune regulation involve the tumor necrosis factor-α (TNF)/TNF receptor (TNFR) pathway. Human immunodeficiency virus 1 (HIV-1) interacts with the TNF/TNFR pathway. The activation of the TNF/TNFR pathway impacts HIV-1 replication, and the TNF/TNFR pathway is the...

A latent viral reservoir that resides in resting CD4+ T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4+...

Although viruses can cause cancer, other studies reported the regression of human tumors upon viral infections. We investigated the cytoreductive potential of human cytomegalovirus (HCMV) in a murine model of human hepatocellular carcinoma (HCC) in severe-immunodeficient mice. Infection of HepG2 cells with HCMV resulted in the absence of tumor or i...

Akt signaling plays a central role in many biological processes, which are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. We found that Akt interacts with HIV-1 Nef protein. In primary T cells treated with exogenous Nef or acutely infected with Nef-expressing HIV-1 in vitro, Akt became phosphorylated on serine(473) and threonin...

Highly active antiretroviral therapy (HAART) has dramatically extended the lifespan and quality of life of individuals infected with human immunodeficiency virus type 1 (HIV-1). HAART comprises of a cocktail of various pharmacological inhibitors which interfere with almost every stages of HIV-1 life cycle. However, constant application of drugs oft...

https://www.ncbi.nlm.nih.gov/nuccore/951504285?report=genbank

With the development of effective combined anti-retroviral therapy (cART), there is significant reduction in deaths associated with human immunodeficiency virus type 1 (HIV-1) infection. However, the complete cure of HIV-1 infection is difficult to achieve without the elimination of latent reservoirs which exist in the infected individuals even und...

Background: Macrophages represent one of the most important human immunodeficiency virus type 1 (HIV-1) cellular reservoirs responsible for the persistence and dissemination of the virus in the infected individuals. PI3K-Akt pathway plays an important role in the cell survival by regulating the expression of several genes. Nef a multi-functional HI...

Eukaryotic translation elongation factors 1 alpha, eEF1A1 and eEF1A2, are not only translation factors but also pleiotropic proteins that are highly expressed in human tumors, including breast cancer, ovarian cancer, and lung cancer. eEF1A1 modulates cytoskeleton, exhibits chaperone-like activity and also controls cell proliferation and cell death....

Human immunodeficiency virus type 1 (HIV-1) establishes latency in resting memory CD4+ T cells and cells of myeloid lineage. In contrast to the T cells, cells of myeloid lineage are resistant to the HIV-1 induced cytopathic effect. Cells of myeloid lineage including macrophages are present in anatomical sanctuaries making them a difficult drug targ...

Sirtuin 1 (Sirt1) is a class III histone deacetylase (HDAC) that modulates gene expression and is involved in the regulation of proinflammatory cytokines. Interleukin-23 (IL-23) is produced by activated macrophages and dendritic cells and could fuel the progression of rheumatoid arthritis (RA). The goal of our study was to evaluate serum IL-23 leve...

Breast cancer is responsible for the majority of the cancer associated death among women in the world. Several chemicals and biological entities have been postulated to trigger cancer including viruses. Human cytomegalovirus (HCMV) is a member of Herpesviridae family, subfamily Betaherpesvirinae. Although the presence of HCMV in human is often unno...

Breast cancer is the leading cause of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses, and therapeutic possibilities....

BACKGROUND: Viruses devise several intelligent strategies to modulate cellular biology and to favor persistent infection. One of such mechanism is apoptosis which is primarily modulated by several human pathogenic viruses. Human immunodeficiency virus type 1 (HIV-1) primarily targets macrophages and CD4+ T cells. HIV-1 Nef protein is expressed duri...

Human cytomegalovirus (HCMV) is a ubiquitous virus which infects 50-90% of the population worldwide. In immunocompetent hosts, HCMV either remains unnoticed or causes mild symptoms. Upon primary infection it establishes latent infection in a few cells. However, in certain situations where immunity is either immature or compromised, HCMV may reactiv...

Breast cancer is the leading causes of cancer-related death among women. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. Numerous articles indicate that breast tumors exhibit diverse phenotypes depending on their distinct physiopathological signatures, clinical courses...

During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication. We performed a ca...

Human immunodeficiency virus type 1(HIV-1) primarily targets macrophages and CD4+ T cells. HIV-1 Nef protein is expressed during early phase of infection and influences nearly all stages of viral growth kinetics. Notably, Nef protects macrophages from stress induced apoptosis triggered upon HIV-1 infection. However, mechanism responsible for Nef in...

Human immunodeficiency virus (HIV) is still a serious global health concern responsible for more than 25 million deaths in last three decades. More than 34 million people are living with HIV infection. Macrophages and CD4+ T cells are the principal targets of HIV-1. The pathogenesis of HIV-1 takes different routes in macrophages and CD4+ T cells. M...

HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of Nef and of the translation elongation factor eEF1A in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t occurs in Nef-trea...

Background: In the recent past, there has been increased concern in the potential involvement of human cytomegalovirus (HCMV) in carcinogenesis. HCMV seroprevalence was enhanced in patients with hepatocellular carcinoma (HCC) however, a possible link between HCC and HCMV infection remains to be assessed. The aim of this work was to investigate the...

Tumor necrosis factor receptor-associated factor (TRAF) signaling plays a central role in many biological activities, such as the regulation of immune and inflammatory responses and control of apoptosis, which are key events in the pathogenesis of the human immunodeficiency virus (HIV)-1 and the hepatitis C virus (HCV) infections. Here we show that...

There has been increased interest in the possible role of human cytomegalovirus (HCMV) in carcinogenesis during the last decade. HCMV seroprevalence was enhanced in patients with hepatocellular carcinoma (HCC) but a possible relationship between HCC and HCMV infection remained to be assessed. The aim of this work was to investigate the pro-tumor in...

Objective: TNF receptor associated factor (TRAF) signaling plays a central role in many biological activities, such as regulation of immune and inflammatory responses and control of apoptosis that are key events in the pathogenesis of human immunodeficiency virus 1 (HIV-1). The Nef protein of HIV-1 is an important factor in AIDS pathogenesis. Nef t...

Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-medi...

Background/Aims: HEV is an emerging pathogen responsible for sporadic and epidemic hepatitis. Etiological agent is a singlestranded positive sense RNA encapsidated in capsid. Viral genome replicates via negative sense intermediate. The dsRNA intermediates can trigger RNAi response against HEV. Thus, presence of RSS in the HEV genome cannot be ruled...

Hepatitis E virus (HEV) is a non-enveloped, single-stranded, positive sense RNA virus, which is a major cause of water-borne hepatitis. RNA interference (RNAi) is a sequence-specific cellular antiviral defence mechanism, induced by double-stranded RNA, which we used to investigate knockdown of several genes and the 3' cis-acting element (CAE) of HE...

Hepatitis E virus (HEV) is a non-enveloped, icosahedral, single-stranded, positive-sense RNA virus, which is the major cause of water borne hepatitis. Till date there is no licensed therapy of vaccine against HEV. Protein based Vaccine which in its Phase III trials has its own demerits. In order to find new approaches for development of new therape...

Hepatitis E virus (HEV) is the major cause of epidemic and many sporadic hepatitis. The virus responsible has a single stranded, positive-sense RNA. Its replication and the regulatory process involved are poorly understood. Much of the HEV biology has been studied using full length capped RNA transcripts (replicons) and transient transfections in c...

Background and Objectives: Hepatitis E virus is the major etiological agent of enterically transmitted hepatitis, and is the major cause of sporadic as well as epidemic hepatitis, which is no longer confined to Asia and developing countries but is also becoming a concern of the developed nations. In India, it accounts for 50-60% of sporadic hepatit...