Marvin Reitz

University of Maryland, Baltimore | UMB · Department of Medicine

Background The chemokine receptor CCR5 is the major coreceptor for HIV-1 cell entry. We previously observed that not all CCR5 mAbs reduce HIV-1 infection, suggesting that only some CCR5 populations are permissive for HIV-1 entry. This study aims to better understand the relevant conformational states of the cellular coreceptor, CCR5, involved in HI...

HIV-1 reservoirs persist in the presence of combined antiretroviral therapy (cART). However, cART has transformed HIV-1 infection into a chronic disease marked by control of HIV-1 viral load and mortality reduction. Major challenges remain, including viral resistance upon termination of cART and persistence and identification of tissue distribution...

Combined antiretroviral therapy (cART) is treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. An estimated 60% of the 38 million HIV-1 patients globally receive some form of cART. The benefits of cART for controlling HIV-1 replication, transmission, and infection rates have led to...

HIV-1 reservoirs persist in the presence of combined antiretroviral therapy (cART). However, cART has transformed HIV-1 infection into a chronic disease marked by control of HIV-1 viral load and mortality reduction. Major challenges remain, including viral resistance upon termination of cART and persistence and identification of tissue distribution...

Several species of mycoplasmas, including Mycoplasma fermentans, are associated with certain human cancers. We previously isolated and characterized in our laboratory a strain of human mycoplasma M. fermentans subtype incognitus (MF-I1) able to induce lymphoma in a Severe Combined Immuno-Deficient (SCID) mouse model, and we demonstrated that its ch...

The efficacy of combined antiretroviral therapy (cART) against HIV-1 is evidenced by reduction of plasma viremia, disease progression, viral transmission and mortality. However, major challenges still remain in HIV-1 management, especially the emergence of resistant strains and the persistence of viral reservoirs, apparent after cART treatment inte...

Despite decades of intensive basic and clinical research efforts, there is still no successful vaccine candidate against human immunodeficiency virus (HIV-1). Standard combined antiretroviral therapy (cART) has been successfully developed and has given remarkable results suppressing HIV-1 infection and transmission. However, cART cannot fully clear...

Significant progress has been made in the diagnostics and treatment of AIDS since the discovery of the human immunodeficiency virus type 1 (HIV-1) in 1983. The remarkable effectiveness of combined antiretroviral therapy (cART) is evidenced by mortality reduction, control of peripheral blood viral load, and in a nearly normal quality of HIV patients...

We have previously shown that FLSC, a chimeric protein containing HIV-1BAL gp120 and the D1 and D2 domains of human CD4 blocks binding and entry of HIV-1 into target cells by occluding CCR5, the major HIV-1 co-receptor. In an effort to improve the antiviral potential of FLSC, we fused it with the hinge-CH2-CH3 region of human IgG1. The IgG moiety s...

Resistance of HIV to drugs compromises the success of ART. Targeting cellular, rather than viral, proteins may delay emergence of HIV resistance as cellular proteins are less likely to mutate under drug pressure than are viral proteins. Cellular P-TEFb, composed of CDK9/cyclin T1, regulates RNA Polymerase II dependent transcription of cellular and...

Host cell proteins offer potential therapeutic targets to inhibit drug-resistant HIV. Indirubin 3'-monoxime (IM) inhibits cellular P-TEFb, which is required for HIV gene expression. We have evaluated IM in humanized mice challenged with multidrug-resistant HIV. IM significantly lowered plasma HIV RNA levels and preserved CD4/CD8 cell ratios. IM tre...

Human Immunodeficiency Virus Type I (HIV-1) infection is associated with a high incidence of B-cell lymphomas. The role of HIV in these lymphomas is unclear and currently there are no valid in vivo models for better understanding HIV-related lymphomagenesis. Transgenic (Tg) 26 mice have a 7.4-kb pNL4-3 HIV-1 provirus lacking a 3.1-kb sequence encom...

Background: Targeting host-cell pathways to increase the potency of nucleoside/nucleotide analog reverse transcriptase inhibitors (NRTIs) is an important strategy for clinical investigation. Resveratrol is a natural product that inhibits cellular ribonucleotide reductase, prolonging the S phase of the cell cycle and preferentially lowering dATP le...

Over the past 10 years, a great deal has been learned about the fundamental biology and therapeutic application of bone marrow-derived human mesenchymal stem cells (MSCs). Intravenous administration of these cells is the preferred route for therapeutic delivery of MSCs. Vascular endothelial cells (ECs) are the first cell type that MSCs encounter fo...

In the past several decades, great progress has been made in our understanding of normal hematopoiesis and its malignant transformation. This article provides a comprehensive and up-to-date review of pathogenesis of leukemia and lymphoma, with an emphasis on early molecular events. Current concepts of normal hematopoiesis and its key regulatory pro...

CCR5 blockers inhibit CCR5-tropic (R5) HIV-1, including strains resistant to other antiretrovirals. We demonstrate that the CCR5 antibody HGS004 and the CCR5 antagonist maraviroc have potent antiviral synergy against R5 HIV-1, translating into dose reductions of more than 10-fold for maraviroc and more than 150-fold for HGS004. These data, together...

R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral ac...

The barrier formed by endothelial cells (ECs) plays an important role in tissue homeostasis by restricting passage of circulating molecules and inflammatory cells. Disruption of the endothelial barrier in pathologic conditions often leads to uncontrolled inflammation and tissue damage. An important component of this barrier is adherens junctions, w...

Maraviroc, the only CCR5 antagonist HIV inhibitor currently approved, has potent antiviral activity in treatment-experienced individuals infected with CCR5-using HIV-1 (R5 HIV-1). However, recent data from the MOTIVATE trials indicate that R5 HIV-1 can develop resistance to Maraviroc, underscoring the need for additional CCR5 antagonists. The CCR5...

Vicriviroc (VCV) is a chemokine (C-C motif) receptor 5 (CCR5) antagonist with potent anti-HIV activity that currently is being evaluated in phase III clinical trials. In the present study, donor CCR5 density (CCR5 receptors/CD4 lymphocytes) inversely correlated with VCV antiviral activity (Spearman's correlation test; r = 0.746, P = 0.0034). Low do...

Summary The genes encoding the envelope glycoprotein H (gH) and gB homologues were identified by sequencing genomic clones of human herpesvirus-7 (HHV-7), strain JI. A gB cDNA clone from HHV-7 strain AL was also identified. The deduced primary translation products of the gH and gB genes are a protein of 690 amino acids, with a predicted mass of 80....

Human immunodeficiency virus (HIV) type 1 infection requires functional interactions of the viral surface (gp120) glycoprotein with cell surface CD4 and a chemokine coreceptor (usually CCR5 or CXCR4) and of the viral transmembrane (gp41) glycoprotein with the target cell membrane. Extensive genetic variability, generally in gp120 and the gp41 ectod...

A potential strategy to combat the worldwide AIDS epidemic is to develop a vaginal microbicide that prevents the sexual transmission of HIV-1. One approach for preventing vaginal HIV transmission is to block the viral coreceptor CCR5 with naturally occurring chemokine ligands. In this study, we used a cynomolgus macaque model to evaluate whether a...

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites...

Local production of macrophage inflammatory protein-1beta (MIP-1beta), a beta-chemokine that blocks human immunodeficiency virus type 1 (HIV-1) entry into CD4+ CC chemokine receptor 5+ target cells, may be a significant factor in resistance to HIV-1 infection and control of local viral spread. The mechanisms governing MIP-1beta expression in T cell...

Oral Presentation.

Human topoisomerase II plays a crucial role in DNA replication and repair. It exists in two isoforms: topoisomerase II alpha (alpha) and topoisomerase II beta (beta). The alpha isoform is localized predominantly in the nucleus, while the beta isoform exhibits a reticular pattern of distribution both in the cytosol and in the nucleus. We show that b...

The HIV-1 Tat protein has been recently explored as a prospective vaccine candidate with broad, subtype non-specific action. We approached the problem of delivery of Tat through the mucosal route by expressing Tat in an edible plant. The tat gene was assembled from synthetic overlapping oligonucleotides, and was subsequently cloned into a plant vir...

Human herpesvirus 8 (HHV-8), also called Kaposi's sarcoma (KS) herpesvirus, can cause KS but is inefficient. Untreated human immunodeficiency virus type 1 (HIV-1) coinfection is a powerful risk factor. The HHV-8 chemokine receptor, vGPCR (ORF74), activates NF-κB and NF-AT, and their levels of activation are synergistically increased by HIV-1 Tat. T...

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4+...

Human and simian immunodeficiency virus (HIV/SIV) Tat proteins are specified by two coding exons. Tat functions in the transcription of primate lentiviruses. A plethora of in vitro data currently suggests that the second coding exon of Tat is largely devoid of function. However, whether the second exon of Tat contributes functionally to viral patho...

The tat, rev, vpu, and env genes from the monocytotropic CCR5-dependent HIV-1 Ba-L isolate were substituted for homologous simian immunodeficiency virus (SIV) sequences in the SIV genome. The resultant SHIV (SHIV Ba-L) replicated in CCR5-positive PM-1 cells but not in CCR5-negative CEMX174 cells. Infection of HOS cells expressing different co-recep...

Human herpesvirus 8 (HHV-8), the etiologic agent of Kaposi's sarcoma (KS), encodes a chemokine receptor homologue, the viral G protein-coupled receptor (vGPCR), that has been implicated in KS pathogenesis. Expression of vGPCR constitutively activates several signaling pathways, including NF-kappa B, and induces the expression of proinflammatory and...

The product of human herpesvirus 8 (HHV-8) open reading frame 74 (ORF74) is related structurally and functionally to cellular chemokine receptors. ORF74 activates several cellular signaling pathways in the absence of added ligands, and NIH 3T3 cells expressing ORF74 are tumorigenic in nude mice. We have generated a line of transgenic (Tg) mice with...

The rational design of new therapies against HIV-1 necessitates an improved understanding of the mechanisms underlying the production of ineffective immune responses to HIV-1 in most infected individuals. This report shows that the CD8(+) T cell responses to gp120 were greatly diminished in mice vaccinated with a bicistronic gp120-Tat DNA vaccine,...

Treatment of patients with human immunodeficiency virus (HIV) protease inhibitors such as ritonavir can result in increases in CD4(+) T-cell counts that are independent of a reduction in HIV-1 viral load. This lack of correlation between the 2 has led to the identification of additional effects of ritonavir that potentially alter HIV disease pathog...

We conducted a national molecular epidemiologic survey of HIV-1 strains in Nigeria to determine the most prevalent subtype(s) for use in developing candidate vaccines. A total of 230 HIV-1-positive blood samples collected from 34 of the 36 Nigerian states were analyzed by our modified env gp41-based heteroduplex mobility assay (HMA) and/or gp41 seq...

We conducted a national molecular epidemiologic survey of HIV-1 strains in Nigeria to determine the most prevalent subtype(s) for use in developing candidate vaccines. A total of 230 HIV-1-positive blood samples collected from 34 of the 36 Nigerian states were analyzed by our modified env gp41-based heteroduplex mobility assay (HMA) and/or gp41 seq...

CD8+ T-cell responses provide beneficial antiviral immunity against human immunodeficiency virus 1 (HIV-1). In this study, we show that intragastric vaccination with a Salmonella HIV-1 Env DNA vaccine vector generates Env-specific CD8+ T-cells, both in mucosal and systemic lymphoid tissue. By contrast, intramuscular vaccination with the Env DNA vac...

Analysis of viral replication and pathogenicity after in vivo selection of human immunodeficiency virus type 1 (HIV-1) attenuated in vitro will help to define the functions involved in replication and pathogenesis in vivo. Using the SCID-hu Thy/Liv mouse and human fetal thymus organ culture as in vivo models, we previously defined HIV-1 env determi...

Infection with human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is necessary for the development of KS. The HHV-8 lytic-phase gene ORF74 is related to G protein-coupled receptors, particularly interleukin-8 (IL-8) receptors. ORF74 activates the inositol phosphate/phospholipase C pathway and the downstream mit...

We report, to our knowledge, the first HIV type 1 (HIV-1) transgenic (Tg) rat. Expression of the transgene, consisting of an HIV-1 provirus with a functional deletion of gag and pol, is regulated by the viral long terminal repeat. Spliced and unspliced viral transcripts were expressed in lymph nodes, thymus, liver, kidney, and spleen, suggesting th...

Depending on the nature of the costimulation of T lymphocytes, expression of regulatory cytokines and chemokines is either susceptible or resistant to cyclic AMP (cAMP)-mediated inhibition. Our data show that cAMP-mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1- and Th 2-like phenotypes, correlat...

The gp120 region of the human immunodeficiency virus type 1 (HIV-1) envelope (env) gene exhibits a high level of genetic heterogeneity across the group M subtypes. The heteroduplex mobility assay (HMA) has successfully been used to assign subtype classifications, but C2V5 primers often fail to amplify African strains. We developed an env gp41-based...