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Overview

The AIDS and Cancer Virus Program (ACVP), formerly the AIDS Vaccine Program (AVP), is an integrated, multidisciplinary program that pursues basic and applied studies aimed at improving our understanding of AIDS-associated viruses, including studies intended to facilitate the improved diagnosis, prevention and treatment of HIV infection and AIDS, and AIDS related tumors, particularly those associated with other viruses such as KSHV. The Program consists of seven independent but highly interactive research Sections headed by Principal Investigators, whose work spans from fundamental molecular virology through in vitro studies, to in vivo studies in non-human primate (NHP) models, to international viral epidemiology.

The Retroviral Evolution Section (RES) under Dr. Brandon Keele, studies various aspects of retroviral transmission, evolution, and immune evasion using sequencing, genetic analyses and molecular biology approaches to better understand the natural course of infection and potential sites and mechanisms of intervention. Dr. Keele¹s laboratory utilizes various nonhuman primate models of AIDS and newly generated viruses to better understand viral/host interactions.

The major research aims for the Retroviral Immunopathology Section (RIPS) under Principal Investigator Dr. Jacob Estes are focused on i) understanding and further elucidating the biology, mechanisms and barriers to lentiviral mucosal transmission and viral dissemination in order to better guide preventative strategies, and ii) to understand the factors driving systemic immune activation and disease progression to guide adjunctive therapeutic intervention strategies that can be used to ameliorate immune activation and its associated pathologic consequences.

The Retrovirus-Cell Interaction Section, under Dr. David Ott, uses molecular and cellular approaches to study processes relevant to retroviral assembly and virion budding. Dr. Ott's laboratory has pioneered approaches for the analysis of cellular proteins associated with retroviruses and factors influencing their incorporation into virions, including development of procedures for obtaining retrovirus preparations of unprecedented purity, and uses proteomic analyses of host cell derived proteins identified in these ultrapure virions to gain insights into the potential involvement of some of these proteins in viral assembly and budding. Dr. Ott's laboratory also utilizes its expertise in retroviral vectors to develop methods for immortalizing and otherwise engineering primary cells of various lineages for experimental objectives.

The Retroviral Immunology Section (RIS), under Dr. Claes Ohlen, studies cellular immune responses to retroviral infection and is exploring the potential of adoptively transferred T lymphocytes in controlling retroviral replication in vivo, using NHP models. Dr. Ohlen's laboratory works closely with Dr. Ott's laboratory using retroviral vectors to engineer cells for experiments exploring mechanisms of effective antiviral T cell responses.

The Retroviral Pathogenesis Section (RPS), under Dr. Jeff Lifson, studies various aspects of retroviral pathogenesis, ranging from in vitro analyses of virus interactions with immune system cells to in vivo studies of retroviral pathogenesis in NHP, including characterization of basic pathogenetic mechanisms and evaluation of novel treatment and prevention modalities. In vivo experiments include efforts to develop improved NHP models for vaccine evaluation and testing of antiretroviral drug treatment and strategies for targeting residual virus and latent reservoirs.

The Viral Oncology Section (VOS), under Dr. Denise Whitby, conducts international molecular and serological epidemiologic studies of infection with KSHV and other viruses, including international projects with a local presence at the Medical Research Council's Uganda Virus Research Institute in Entebbe, Uganda, along with basic studies of KSHV biology, with a recent emphasis on the role of miRNA.

The Program also includes eight Research Support Core Groups (Cores) that provide critical and often unique technical support capabilities to ACVP laboratories and other laboratories within the NCI and NIH, and to extramural investigators.

The Quantitative Molecular Diagnostics Core (QMDC), under Dr. Michael Piatak, Jr., develops and applies state of the art quantitative PCR and RT PCR methods for quantitative analysis of specific DNA and RNA species relevant to retrovirology and AIDS studies, emphasizing NHP models. The QMDC is in the process of expanding its capabilities to also handle specialized analyses for HIV-1 specimens in a new HIV Molecular Monitoring Core (HMMC, see below).

The Biological Products Core (BPC), under Mr. Julian Bess, Jr., performs multi-scale production (30ml to 30L per batch), chemical inactivation treatment (if desired), purification, and associated quality control analyses of retroviruses and related control reagents (microvesicles) that are used as vaccine immunogens for animal studies and as key reagents for various in vitro studies. Fluorescently labeled retrovirus and microvesicle preparations can also be prepared. The BPC also prepares and distributes antigen capture immunoassay kits for the cost effective measurement of HIV p24 antigen from in vitro samples.

The Retroviral Protein Chemistry Core (RPCC), under Dr. Elena Chertova, maintains a cutting edge capability for detailed analysis of viral proteins and host cell proteins associated with retroviruses, continuing to refine analytical methods such as microscale HPLC fractionation and sensitive sequence and mass spectrometry based analysis of viral and host cell proteins from highly purified preparations of retroviruses. With Dr. Gorelick’s RMS the RPCC provides highly purified, well characterized recombinant retroviral NC proteins to intramural and extramural investigators around the world, that are recognized as the gold standard in the field.

The Specimen Support Core (SSC), under Dr. Greg Del Prete, serves as the "clinical laboratory" equivalent for specimens associated with studies in NHP conducted by ACVP scientists and collaborators. The SSC receives, accessions, processes, distributes, and stores blood and tissue derived specimens from macaques under study, and maintains detailed databases on these specimens, including current inventories of cryopreserved samples, and also performs standardized assays on these samples.

The Cellular Immunity Core (CIC), under Mr. Mac Trubey, consolidates the cellular immunology instrumentation and capabilities of the program in support of ACVP investigators and collaborators, with advanced multiparameter flow cytometry analysis and fluorescence activated cell sorting capabilities, including the capacity for sorting of infectious specimens under appropriate biocontainment conditions.

The Tissue Analysis Core (TAC), under Dr. Jake Estes, provides state of the art tissue based analyses relevant to the study of retroviral pathogenesis and related questions, employing various in situ hybridization, immunofluorescence, and immunohistochemistry methods, including multi-label studies and laser capture microdissection based analysis, along with advanced image analysis capabilities.

The Viral Evolution Core (VEC), under Dr. Brandon Keele, provides access to cutting edge sequence based analysis, including both single genome amplification sequencing techniques and high throughput pyrosequencing technology, coupled with genetic analyses. These approaches are useful for characterization of virus stocks used for NHP studies, for evaluation of virus during transmission and subsequent evolution, and for efficacy assessment of various intervention modalities.