reduced immune activation, might attenuate infection of memory T cell subsets and preserve critical CD4 T cell homeostasis. Methods: Levels of plasma cytokines at seroconversion were measured using a Luminex platform. Flow cytometry was used to assess markers of activation (CD38 + HLADR + ), exhaustion (PD-1 and CD57), and proliferation (Ki-67) on CD4 and CD8 cells. Cell associated viral DNA in CD4 memory populations was quantified with qPCR. Results: RC was positively correlated with levels of inflam- matory cytokines in plasma and with activation of both CD8 (p = 0.01) and central memory (CM) CD4 T cells (p = 0.002). Low RC was associated with CD8 T cells that were less ex- hausted (p < 0.001) and more cytotoxic (p = 0.002). RC was positively correlated with proliferation (p = 0.003) and with the level of cell associated viral DNA in CM CD4 T cells (p = 0.01), a population highlighted to be integral for the maintenance of latency and preferentially spared in non-pathogenic SIV infec- tion. Consistent with previous studies, we observed that cellular immune activation, proliferation, exhaustion, and cell associated viral DNA in CM CD4 T cells were all associated with the rate of disease progression. Conclusions: This study highlights the integral role that RC of the transmitted virus plays in defining several facets of HIV-1 immunopathology. Understanding the complex interactions be- tween HIV and the immune system will be crucial for designing innovative prevention strategies. JP and DC contributed equally to this work OA21.04 In Vitro Fitness of HIV-1 Transmitted/Founder versus Non-transmitted Full-length Genome Infectious Molecular Clones Martin J. Deymier 1 , Zachary Ende 1 , Daniel T. Claiborne 1 , William Kilembe 2 , Susan Allen 1,2 , Eric Hunter 1,2 1 Emory University, Atlanta, GA, United States, 2 Zambia Emory HIV Research Program, Lusaka, Zambia Background: In *80% of heterosexual transmissions of HIV-1, an infected individual with a diverse viral quasispecies trans- mits a single viral variant, the Transmitted/Founder (TF), to a naı ¨ve host. Evidence is building that TF variants are enriched for certain genetic and phenotypic characteristics that pre- sumably enhance the efficiency of transmission. However, the mechanisms involved are largely ambiguous, partially because studies using full-length genomes in transmission pairs are lacking. Methods: We have performed HIV near full-length (NFL) single genome amplification from six subtype C acutely in- fected individuals and each of their chronically infected viro- logically linked partners in the Zambia-Emory HIV Research Project. Phylogenetic analysis performed on the 118 NFL ge- nomes (mean 18/transmission pair) confirms epidemiologically linked transmission as well as infection by a single viral variant in each case. We have generated 5 TF & 34 non-transmitted (NT) full-length infectious molecular clones from 5 transmis- sion pairs and assayed for particle infectivity by dividing the virus titer on TZM-bl cells by the RT activity of the virus stock. Results: The particle infectivity of the TF compared to the median of the NT variants for all matched transmission pairs was not statistically significant (p = 0.22). However, particle infec- tivity correlated with the amount of glycosylation on the Env V1-V4 region (R = 0.40, p = 0.01) as well as with replication in PBMCs for a subset of tested viruses (R = .823 p = 0.01), sug- gesting that previous findings showing less glycosylation on TF viruses could mean lower replicative capacities in vitro. How- ever, preliminary data suggests that lower replicating, less gly- cosylated viruses, may preferentially productively infect monocyte-derived dendritic cells. Conclusions: Understanding the characteristics of TF viruses that allow for efficient transmission will aid in prophylaxis and early intervention efforts. OA21.05 Genetic Footprints within the HIV-1 Envelope Glycoprotein Associated with Transmission in Men Who Have Sex with Men Damien C. Tully 1 , Colin B. Ogilvie 1 , Rebecca Batorsky 1 , Karen A. Power 1 , Hunter Bedard 1 , Aaron Seese 1 , Molly Amero 1 , Sue Bazner 2 , Jake Tinsley 3 , Niall J. Lennon 4 , Matthew R. Henn 4 , Eric Rosenberg 2 , Kenneth H. Mayer 3 , Heiko Jessen 5 , Marcus Altfeld 1,6 , Todd M. Allen 1 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States, 2 Massachusetts General Hospital, Infectious Disease, Boston, MA, United States, 3 The Fenway Institute, Fenway Health, Boston, MA, United States, 4 The Broad In- stitute of MIT and Harvard, Cambridge, MA, United States, 5 HIV Clinic Praxis, Jessen, Berlin, Germany, 6 Heinrich-Pette- Institut, Viral Immunology, Hamburg, Germany Background: The global spread of HIV - 1 has been fueled by sexual transmission with the epidemic disproportionately af- fecting men who sex with men (MSM). As the epidemic in MSM continues unabated, understanding the virus-host inter- actions responsible for transmission may be critical for the de- velopment of an HIV vaccine and other prevention strategies. Methods: To elucidate the nature of the transmitted/founder (TF) virus following rectal transmission, we developed a novel analytical strategy utilizing deep sequencing data from a cohort of 67 acutely infected MSM subjects. Results: Empirical analyses revealed that deep sequencing could not only reliably infer the TF virus but also discriminate between single and multiple HIV infections. Using this approach we found that most transmissions resulted from a single infec- tion with only 16% of individuals exhibiting evidence of mul- tiple variant transmissions. We extended this study to identify signature mutations that may be favored at transmission between viruses originating from heterosexual exposure versus those from MSM. Here, we focused on a comprehensive analysis of Env sequences from 125 early subjects (Fiebig I-III) to discern the genetic imprint on the underlying composition of the viral quasispecies. A number of genetic signatures were identified in gp120 and the gp41 cytoplasmic tail. One signature pattern specifically enriched in TF viruses from MSM was the loss of an N-linked glycosylation site at position 362 in the C3 region adjacent to the CD4 binding site. The loss of this glycosylation motif has previously been associated with chronic infection and implicated in increased cell-to-cell fusion activity and a high apoptosis inducing phenotype. Conclusions: Taken together, these findings provide unique insight into the events of early transmission in MSM and reveal potentially important mechanistic differences that may exist between the different routes of sexual transmission that are not yet fully understood. A57