Currently there are approximately 33.4 million people living with HIV-1 worldwide and it is estimated that every year AIDS claims about 2-3 million deaths while HIV-1 is responsible for an equal number of new infections. In spite of the advances in the fight against HIV-1 since the isolation of the virus in 1983, there is still no vaccine available for the prevention of HIV-1 infection, and so far the available therapies have failed to eradicate the virus. The use of animal models for the development of vaccines, testing of new antiviral drugs, and studies of pathogenesis has been invaluable. The presence of several barriers to HIV-1 replication in cells of many species narrows the species tropism of HIV-1 to humans and chimpanzees. The most widely used animal model for AIDS is the infection of Asian macaques by simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) chimerae. The development of models in which the host animal can be infected with more HIV-1-like viruses is a worthy goal. Such a new animal model would be useful for studying viral pathogenesis and for testing antiviral therapies and vaccines. Here, we propose to study the host cell restriction factors that block the replication of HIV-1 in common marmoset cells, with the long term goal of developing a new animal model for HIV-1 infection using the common marmoset, a New World monkey, as a host animal.