Research Interests and Goals

The Virus-Cell Interaction Section, under the direction of Eric O. Freed, is interested in the assembly and release of HIV-1 from infected cells, Env incorporation, the host factors that both promote and restrict the late events in HIV-1 replication, and virus maturation.  Dr. Freed has a long-term program focused on developing maturation inhibitors, and his group recently discovered a role for HIV-1 Env in broadly rescuing blocks to virus replication in vitro, including those conferred by antiretrovirals.

The Antiviral Immunity and Resistance Section, led by Alex Compton, combines approaches in virology, cell biology, and evolutionary biology to study cell-intrinsic mechanisms of virus defense.  Dr. Compton has made major contributions to our understanding of the antiviral activity of the IFITM protein family in the context of HIV-1, influenza A, and Zika virus infections and discovered regulatory mechanisms that control IFITM protein expression, which can be exploited for lentiviral vector-mediated gene delivery.  Most recently, this Section is investigating roles for the IFITM proteins during cancer development. 

The Viral Recombination Section, directed by Wei-Shau Hu, studies how HIV transfers genetic information to its progeny.  This Section combines state-of-the-art microscopy techniques with sophisticated virology and molecular biology approaches to study RNA genome packaging, virus assembly, and the biology of the full-length RNA.  Dr. Hu also uses model systems and clinical isolates to study the mechanisms of reverse transcription, recombination, and virus evolution. 

•  The Translational Research Section, under the direction of Mary F. Kearney, analyzes viral RNA and DNA sequences present in cells and plasma.  This Section performs studies of HIV genetics in individuals, viral persistence during therapy, and the development and evolution of drug resistance.

The Clinical Retrovirology Section, headed by Frank Maldarelli, uses clinical protocols at the NIH Clinical Center to investigate how HIV infections persist even after years of successful antiretroviral therapy (ART) and what constitutes the reservoir of infected cells that leads to reemergence of the virus if ART is interrupted or inadequate.  The Section also studies the population genetics of HIV prior to and following initiation of ART to understand the emergence of resistance within individuals.  Dr. Maldarelli divides his time between the Bethesda campus of the NIH, where he works in conjunction with the NIAID/CCMD AIDS clinical program and the NCI HIV and /AIDS Malignancy Branch, and the Frederick campus, where his laboratory is located.

The Viral Mutation Section, headed by Vinay K. Pathak, focuses on elucidating the early stages of HIV-1 replication by developing new imaging tools and methods to analyze early replication events, including nuclear import, intranuclear transport and nuclear localization, uncoating, and proviral transcription.  This Section also focuses on elucidating the structure and function of HIV-1 Vif and APOBEC3 restriction factors and developing new gene therapy strategies for HIV-1 treatment and functional cure. 

The Retrovirus Assembly Section, headed by Alan Rein, investigates virus assembly and maturation, with a focus on human and murine retroviruses.  Other research interests include structure-function relationships in viral proteins and viral RNA, retrovirus biology, and cellular defense mechanisms against retroviruses, such as restriction by SERINC5 and APOBEC3.

•  The Tumor Virus RNA Biology Section, under the direction of Zhi-Ming (Thomas) Zheng, is interested in viral and host gene expression and posttranscriptional regulation.  Using papillomaviruses and Kaposi’s sarcoma-associated herpesvirus as model virus systems, this Section has pursued a long-term focus on how protein-nucleic acid and protein-protein interactions regulate the transcription of viral and host genes, RNA splicing and polyadenylation, RNA stability, export, and translation in the context of viral infections and carcinogenesis. 

The HIV DRP is a research program of the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), National Institutes of Health (NIH).