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Lack of Evidence for Molecular Mimicry in HIV-Infected Subjects

Previous studies in HIV patients have reported autoantibodies to several human proteins, including erythropoietin (EPO), interferon-α (IFN-α), interleukin-2 (IL-2), and HLA-DR, as potential mediators of anemia or immunosuppression. The etiology of these autoantibodies has been attributed to molecular mimicry between HIV epitopes and self-proteins. Here, the Luciferase...

Pneumocystis Encodes a Functional Endo-β-1,3-glucanase That is Expressed Exclusively in Cysts

β-1,3-glucan is a major cell wall component of Pneumocystis cysts. We have characterized endo-β-1,3-glucanase (Eng) from 3 species of Pneumocystis. The gene eng is a single-copy gene that encodes a protein containing 786 amino acids in P. carinii and P. murina, and 788 amino acids in P. jirovecii, including a signal peptide for the former 2 but not the latter. Recombinant Eng...

Expression of Pneumocystis jirovecii Major Surface Glycoprotein in Saccharomyces cerevisiae

Geetha Kutty 0 Katherine J. England 0 Joseph A. Kovacs 0 0 Critical Care Medicine Department, National Institutes of Health (NIH) Clinical Center , NIH, Bethesda, Maryland The major surface

Discordant antibody and cellular responses to Pneumocystis major surface glycoprotein variants in mice

BackgroundThe major surface glycoprotein (Msg) of Pneumocystis is encoded by approximately 50 to 80 unique but related genes. Msg diversity may represent a mechanism for immune escape from host T cell responses. We examined splenic T cell proliferative and cytokine as well as serum antibody responses to recombinant and native Pneumocystis antigens in immunized or Pneumocystis...

HIV Antibody Characterization as a Method to Quantify Reservoir Size During Curative Interventions

Quantitative humoral profiling of recent samples from a human immunodeficiency virus (HIV)–infected adult who was cured following a delta32/delta32 CCR5 stem cell transplant in 2007 revealed no antibodies against p24, matrix, nucleocapsid, integrase, protease, and gp120, but low levels of antibodies against reverse transcriptase, tat, and gp41. Antibody levels to these HIV...

The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma

Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy...

Variation in the Major Surface Glycoprotein Genes in Pneumocystis jirovecii

The genome of Pneumocystis, which causes life-threatening pneumonia in immunosuppressed patients, contains a multicopy gene family that encodes the major surface glycoprotein (Msg). Pneumocystis can vary the expressed Msg, presumably as a mechanism to avoid host immune responses. Analysis of 24 msg-gene sequences obtained from a single human isolate of Pneumocystis demonstrated...

Lack of Compartmentalization of HIV-1 Quasispecies Between the Gut and Peripheral Blood Compartments

Compartmental differences in human immunodeficiency virus type 1 (HIV-1) between the gut and peripheral blood and within the gut were examined. Biopsy specimens from the colon and ileum and peripheral blood samples were collected from chronically HIV-1–infected individuals. HIV-1 envelope sequences were examined from cell-associated DNA and RNA and virion RNA. Phylogenetic...

Altered Antibody Profiles against Common Infectious Agents in Chronic Disease

Joseph A. Kovacs 0 Michael J. Iadarola 0 Stefan Bereswill, Charit-University Medicine Berlin, Germany 0 1 Clinical Dental Research Core, National Institute of Dental and Craniofacial Research, National

Nucleic Acid Amplification Tests for Diagnosis of Smear-Negative TB in a High HIV-Prevalence Setting: A Prospective Cohort Study

Background Nucleic acid amplification tests are sensitive for identifying Mycobacterium tuberculosis in populations with positive sputum smears for acid-fast bacilli, but less sensitive in sputum-smear-negative populations. Few studies have evaluated the clinical impact of these tests in low-income countries with high burdens of TB and HIV. Methods We prospectively enrolled 211...

Quantitation of Anti–Pneumocystis jiroveci Antibodies in Healthy Persons and Immunocompromised Patients

To facilitate studies of the epidemiology of Pneumocystis jiroveci infection in both healthy persons and immunocompromised patients, we developed a quantitative ELISA with recombinant major surface glycoprotein (MSG) fragment MSG-14, a P. jiroveci–specific protein that includes a highly conserved region of the MSG protein family. By immunoblot, all samples reacted with the...

Distinct profiles of antibodies to Kaposi sarcoma-associated herpesvirus antigens in patients with Kaposi sarcoma, multicentric Castleman’s disease, and primary effusion lymphoma

primary effusion lymphoma Peter D Burbelo 0 Alexandra T Issa 0 Kathryn H Ching 0 Kathleen M Wyvill Richard F Little Michael J Iadarola 0 Joseph A Kovacs Robert Yarchoan From th International Conference on

Outbreaks of Pneumocystis Pneumonia in 2 Renal Transplant Centers Linked to a Single Strain of Pneumocystis: Implications for Transmission and Virulence

Background.  There have been numerous reports of clustered outbreaks of Pneumocystis pneumonia (PCP) at renal transplant centers over the past 2 decades. It has been unclear whether these outbreaks were linked epidemiologically to 1 or several unique strains, which could have implications for transmission patterns or strain virulence. Methods.  Restriction fragment length...

Distinct Profiles of Antibodies to Kaposi Sarcoma-Associated Herpesvirus Antigens in Patients with Kaposi Sarcoma, Multicentric Castleman Disease, and Primary Effusion Lymphoma

Antibody responses against lytic and latent Kaposi sarcoma (KS)—associated herpesvirus antigens were investigated in patients with KS, multicentric Castleman disease (MCD), and primary effusion lymphoma. Antibodies against the lytic antigen K8.1 were 5-fold higher in patients with MCD than those with KS, whereas antibodies to the sum of latent antigens v-cyclin and LANA were 27...

Proteome-Wide Anti-Hepatitis C Virus (HCV) and Anti-HIV Antibody Profiling for Predicting and Monitoring the Response to HCV Therapy in HIV-Coinfected Patients

We quantified antibody responses to the hepatitis C virus (HCV) proteome that are associated with sustained virologic response (SVR) in human immunodeficiency virus (HIV)/ HCV–coinfected patients treated with pegylated interferon and ribavirin. Analysis of pre- and posttreatment samples revealed significant decreases in the combined anti-core, anti- E1, and anti-NS4 HCV antibody...

Restriction Fragment Length Polymorphism Typing Demonstrates Substantial Diversity among Pneumocystis jirovecii Isolates

Better understanding of the epidemiology and transmission patterns of human Pneumocystis should lead to improved strategies for preventing Pneumocystis pneumonia (PCP). We have developed a typing method for Pneumocystis jirovecii that is based on restriction fragment length polymorphism (RFLP) analysis after polymerase chain reaction amplification of an ∼1300 base-pair region of...

Genetic Divergence of the Dihydrofolate Reductase and Dihydropteroate Synthase Genes in Pneumocystis carinii from 7 Different Host Species

. Kovacs 2 0 Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki , Helsinki , Finland 1 Science Applications International Corporation , Frederick, Maryland , USA

The Incidence and Natural History of Osteonecrosis in HIV-Infected Adults

Background. Osteonecrosis is increasingly recognized as a debilitating complication of human immunodeficiency virus (HIV) infection, but the natural history has not been well described. We previously documented a high prevalence (4.4%) of magnetic resonance imaging (MRI)–documented osteonecrosis of the hip in a cohort of 339 asymptomatic HIV-infected patients. The present study...