The Retroviral Replication Laboratory (RRL) focuses on obtaining a detailed understanding of important events in the life cycle of human retroviruses, with a primary focus on HIV-1, from the initial interactions between the virion and the host cell through reverse transcription and integration to mechanisms of virus assembly and release. There is extensive work on the biochemistry and biology of viral replication, drug resistance, recombination, and the generation of mutations. Studies also include discovery, development, and mechanistic analysis of novel replication inhibitors, as well as whole-organism studies, including development of important animal models, and the development and use of retroviral vectors. The RRL is composed of six Sections: The Vector Design and Replication Section, directed by Dr. Stephen H. Hughes, has two principal areas of research interest: 1) HIV-1 reverse transcriptase (RT); and 2) HIV-1 integrase. The Retrovirus Assembly Section, led by Dr. Alan Rein, has been focusing primarily on the roles of elements of the Gag protein, nucleic acid, and host factors in virus assembly. The Virus-Cell Interaction Section, under the direction of Dr. Eric O. Freed, is well known for its work on the assembly and release of HIV-1 from infected cells and the host factors essential for efficient assembly and release. The Viral Recombination Section, directed by Dr. Wei-Shau Hu, focuses on mechanisms of recombination, RNA packaging, and virus assembly. The Viral Mutation Section, headed by Dr. Vinay K. Pathak, focuses on in vivo mechanisms of reverse transcription, APOBEC, RT template switching, and how mutations in the C-terminal portion of RT contribute to resistance to both nucleoside RT inhibitors (NRTIs) and nonnucleoside RT inhibitors (NNRTIs). The Antiviral Immunity and Resistance Section, led by Dr. Alex Compton, focuses on mechanisms of protection mediated by the cell-intrinsic innate immune response, as well as the strategies employed by HIV and emerging viruses to evade or overcome these immune barriers.