The HIV DRP comprises a basic research component (Retroviral Replication Laboratory, RRL) and a clinical/translational component (Host-Virus Interaction Branch, HVIB).
The RRL focuses on understanding events in the viral replication cycle, from the initial interactions of the virus and host cell; through reverse transcription, nuclear import, and integration; to RNA trafficking, virus assembly, release, and maturation. Studies also focus on host restriction factors, antiviral immunity, and genetic variation and evolution of HIV and other viruses, particularly viruses that can cause cancer in humans.
• 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 Vector Design and Replication Section, directed by Stephen H. Hughes, has two principal areas of research: developing inhibitors to HIV-1 reverse transcriptase and integrase, and elucidating the link between HIV-1 integration sites in infected individuals and viral persistence in vivo.
• 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 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 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 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 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 HVIB carries out translational and clinical studies to elucidate HIV-host interactions and to devise approaches to understand, and eventually eliminate, HIV reservoirs. This Branch has studied the evolution and clinical significance of HIV drug resistance in vivo, and the persistence of HIV-infected cells in individuals on antiretroviral therapy (ART). The HVIB contains two research sections, headed by Frank Maldarelli and Mary F. Kearney. Stephen Hughes serves as Chief of the HVIB and is engaged in extensive collaborative interactions with this Branch. John W. Mellors and John M. Coffin, through contracts with the University of Pittsburgh and Tuft University, respectively, also play important roles in the research mission of the HVIB.
• 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 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 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.