Despite the development of more than 20 antiretrovirals in the last 30 years, HIV-1 continues to be one of the major infectious causes of mortality in the world. Due to invasive side effects and the high cost of antiretrovirals novel treatment strategies are in high demand. One of the strategies for targeting viral infection with drug intervention takes advantage of the fact that HIV-1 requires host cell machinery to complete its life cycle. Identifying host cell factors that are involved in HIV-1 life cycle as well as elucidating the roles they play in viral infection can lead to discovery of potential drug targets. In this dissertation my goal is to understand the role of some host cell processes in the replication cycle of HIV-1. I approached this in two ways: In the first two parts I studied the role of a ubiquitous cellular pathway called the N-end rule pathway in the early phase of the retroviral life cycle. In the third part I have characterized a human cell line that was found to be non-permissive to infection with retroviruses and retroviral vectors.