A major challenge in finding cure for HIV infection is to eliminate viral reservoirs. Memory CD4 T cells, as the primary reservoir, are preferentially infected by HIV. However, this preference is not currently understood. G protein behaves as an essential molecular switch in cellular signaling. Its diversity promotes the signaling variation in different cell types. Based on previous studies, we hypothesized that differences in G protein signaling from the chemokine coreceptors may play an important role in affecting HIV infection. In this study, we successfully developed a standard assay that can profile multiple G proteins in HIV infected T cells. Through this system, we also identified major differences in G protein expression profiles among various human cell types, especially human naive and memory CD4 T cells. This research established a vital tool in understanding the cellular environment permitting HIV persistence.