AIDS and Cancer Virus Program
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
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 Ms.
Rebecca Kiser, 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
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