Cytokine levels in breast cancer are highly dependent on cytomegalovirus (CMV) status.

Purpose: Breast cancer accounts for 30% of all female cancers in the US. Cytomegalovirus (CMV), a herpesvirus that establishes lifelong infection, may play a role in breast cancer. CMV is not oncogenic, yet viral DNA and proteins have been detected in breast tumors, indicating possible contribution to tumor development.

Herpes Simplex Virus: A Versatile Tool for Insights Into Evolution, Gene Delivery, and Tumor Immunotherapy.

Herpesviruses are prevalent throughout the animal kingdom, and they have coexisted and coevolved along with their host species for millions of years. Herpesviruses carry a large (120-230 kb) double-stranded DNA genome surrounded by a protein capsid, a tegument layer consisting of viral and host proteins, and a lipid bilayer envelope with surface glycoproteins. A key characteristic of these viruses is their ability to enter a latent state following primary infection, allowing them to evade the host's immune system and persist permanently.

Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV).

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease.

Control of Cytokines in Latent Cytomegalovirus Infection.

Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection.

Identification of a novel signaling complex containing host chemokine receptor CXCR4, Interleukin-10 receptor, and human cytomegalovirus US27.

Human cytomegalovirus (HCMV) is a widespread herpesvirus that establishes latency in myeloid cells and persists by manipulating immune signaling. Chemokine receptor CXCR4 and its ligand CXCL12 regulate movement of myeloid progenitors into bone marrow and out into peripheral tissues. HCMV amplifies CXCL12-CXCR4 signaling through viral chemokine receptor US27 and cmvIL-10, a viral cytokine that binds the cellular IL-10 receptor (IL-10R), but precisely how these viral proteins influence CXCR4 is unknown.

Who Let the Dogs Out? A Plea for Official Guidelines on Service Animals in the Teaching Laboratory.

Microbiology teaching labs provide the opportunity for students to develop marketable skills while observing the microbial inhabitants of our planet as they grow, ferment, and produce colorful by-products. Emphasizing safe laboratory practices is an essential part of this education, but occasionally situations that challenge safety paradigms arise. We describe here a recent incident in which a student brought a guide dog-in-training to her microbiology lab, causing a scramble to provide "reasonable" accommodations.

The Human Cytomegalovirus US27 Gene Product Constitutively Activates Antioxidant Response Element-Mediated Transcription through Gγ, Phosphoinositide 3-Kinase, and Nuclear Respiratory Factor 1.

Human cytomegalovirus (HCMV) is a widespread pathogen that modulates host chemokine signaling during persistent infection in the host. HCMV encodes four proteins with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs): US27, US28, UL33, and UL78. Each of the four receptors modulates host CXCR4 signaling.

Human Cytomegalovirus UL111A and US27 Gene Products Enhance the CXCL12/CXCR4 Signaling Axis via Distinct Mechanisms.

Human cytomegalovirus (HCMV) is a prevalent pathogen that establishes lifelong infection in the host. Virus persistence is aided by extensive manipulation of the host immune system, particularly cytokine and chemokine signaling pathways. The HCMV UL111A gene encodes cmvIL-10, an ortholog of human interleukin-10 that has many immunomodulatory effects.

Modulation of the Host Environment by Human Cytomegalovirus with Viral Interleukin 10 in Peripheral Blood.

Background: Human cytomegalovirus (HCMV) is a herpesvirus with both lytic and latent life cycles. Human cytomegalovirus encodes 2 viral cytokines that are orthologs of human cellular interleukin 10 (cIL-10). Both cytomegalovirus interleukin 10 (cmvIL-10) and Latency-associated cytomegalovirus interleukin 10 (LAcmvIL-10) (collectively vIL-10) are expressed during lytic infection and cause immunosuppressive effects that impede virus clearance.

Evolution of the ability to modulate host chemokine networks via gene duplication in human cytomegalovirus (HCMV).

Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skillful at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host. One aspect of this co-evolution involves the acquisition of virally encoded G protein-coupled receptors (GPCRs) with homology to the chemokine receptor family. GPCRs are the largest family of cell surface proteins, found in organisms from yeast to humans, and they regulate a variety of cellular processes including development, sensory perception, and immune cell trafficking.

Human cytomegalovirus interleukin-10 enhances matrigel invasion of MDA-MB-231 breast cancer cells.

Background: While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells.

Effect of human cytomegalovirus (HCMV) US27 on CXCR4 receptor internalization measured by fluorogen-activating protein (FAP) biosensors.

Human cytomegalovirus (HCMV) is a widespread pathogen and a member of the Herpesviridae family. HCMV has a large genome that encodes many genes that are non-essential for virus replication but instead play roles in manipulation of the host immune environment. One of these is the US27 gene, which encodes a protein with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs).

Viral manipulation of the host immune response.

Viruses are obligate intracellular parasites that require a host for essential machinery to replicate and ultimately be transmitted to new susceptible hosts. At the same time, the immune system has evolved to protect the human body from invasion by viruses and other pathogens. To counter this, viruses have developed an arsenal of strategies to not only avoid immune detection but to actively manipulate host immune responses to create an environment more favorable for infection.

Human Cytomegalovirus interleukin-10 promotes proliferation and migration of MCF-7 breast cancer cells.

Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the family that is widespread in the general population and has been linked to several forms of cancer.

The DRY box and C-terminal domain of the human cytomegalovirus US27 gene product play a role in promoting cell growth and survival.

Human cytomegalovirus (HCMV) is a widespread pathogen that can lay dormant in healthy individuals and establish lifelong latent infection. This successful co-existence is facilitated by a number of viral gene products that manipulate host cellular functions and immune responses. Among these immunomodulatory genes are four G-protein coupled receptors (GPCRs) encoded by HCMV, designated US27, US28, UL33, and UL78.

CXCR4: a virus's best friend?

Viruses are dependent on their hosts for replication and dispersal in the environment; thus, the most successful viruses are those that co-evolve with their hosts. CXCR4 is a cellular chemokine receptor that plays central roles in development, hematopoiesis, and immune surveillance through signaling induced by its ligand, CXCL12. The CXCR4-CXCL12 axis has been besieged by many pathogens that employ a range of strategies to modify or exploit CXCR4 activity.

cmvIL-10 stimulates the invasive potential of MDA-MB-231 breast cancer cells.

Cancer is the result of unregulated cell growth that leads to tumor formation, and in many cases, metastases. Although there are several risk factors associated with cancer, one area that remains poorly understood is the impact of infectious disease. Human cytomegalovirus (HCMV) is a member of the herpesvirus family that is highly prevalent in the population.

The human cytomegalovirus US27 gene product enhances cell proliferation and alters cellular gene expression.

Human cytomegalovirus (HCMV) is a prevalent pathogen worldwide. Although generally harmless in healthy individuals, HCMV can pose a serious threat to immune compromised individuals and developing fetuses in utero. HCMV encodes four genes predicted to give rise to G protein-coupled receptors (GPCRs): US27, US28, UL33, and UL78.

The US27 gene product of human cytomegalovirus enhances signaling of host chemokine receptor CXCR4.

Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that manipulates host immune responses and establishes life-long latent infection, in part through mimicry of cytokines, chemokines, and chemokine receptors. The HCMV US27 gene product is a putative chemokine receptor with no known ligands. We generated a stable US27 cell line to screen for chemokine ligands but unexpectedly found that US27 potentiated the activity of an endogenous human chemokine receptor, CXCR4.

Receptor chimeras demonstrate that the C-terminal domain of the human cytomegalovirus US27 gene product is necessary and sufficient for intracellular receptor localization.

Background: Human cytomegalovirus (HCMV) is ubiquitous in the population but generally causes only mild or asymptomatic infection except in immune suppressed individuals. HCMV employs numerous strategies for manipulating infected cells, including mimicry of G-protein coupled receptors (GPCRs). The HCMV US27 gene product is a putative GPCR, yet no ligand or signaling has been identified for this receptor.

Antibodies to human IL-10 neutralize ebvIL-10-mediated cytokine suppression but have no effect on cmvIL-10 activity.

Interleukin-10 is a pivotal determinant of virus clearance or persistence. Two human herpesviruses, Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) are unique among persistent viruses because they not only trigger production of host IL-10, but both viruses also encode homologs of IL-10 that are expressed during infection. Because anti-human IL-10 antibodies have diagnostic value and therapeutic potential for many chronic infections, cross-reactivity with ebvIL-10 and cmvIL-10 was evaluated in this study.

HCMV IL-10 suppresses cytokine expression in monocytes through inhibition of nuclear factor-kappaB.

Modulation of host immune responses is a common strategy for promoting virus persistence and avoiding clearance. Human cytomegalovirus (HCMV) is known to encode numerous immunomodulatory genes, including a homolog of the cytokine human interleukin-10 (hIL-10). While having limited sequence homology to hIL-10, cytomegalovirus IL-10 (cmvIL-10) shares many functional characteristics with the human cytokine and acts as a potent suppressor of the inflammatory immune response.