CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: Co-infection with HIV-1 and HTLV-1 produces naturally pseudotyped HIV-1 capable of directly infecting primary female lower genital epithelial cells and that the pseudotyped HIV-1 may be resistant to RT inhibitors.

WEDNESDAY, FEBRUARY 25, 2015 Session P-A5 Poster Session

Poster Hall

2:30 pm– 4:00 pm Envelopes, Receptors, and Tropism 215 Evaluation of HIV-1 Clones for Unique Properties AssociatedWith Transmission Katja Klein 1 ; Annette Ratcliff 2 ; Gabrielle Nickel 2 ; Immaculate Nankya 2 ; Mike Lobritz 2 ;Yong Gao 2 ; Robin Shattock 3 ; Eric J. Arts 1 1 University of Western Ontario, London, Canada; 2 Case Western Reserve University, Cleveland, OH, US; 3 Imperial College London, London, United Kingdom

Poster Abstracts

Background: In the vast majority of cases, mucosal HIV-1 infection is initiated by a single infectious virus or a small number of HIV-1 virions. Next to CCR5 receptor usage and envelope glycosylation, little is known about the phenotypic properties of these transmitted HIV-1 virions and the influence that phenotype plays in the genetic bottleneck selection process. We evaluated a number of acute/early and chronic HIV-1 viruses, isolated from the female genital tract and blood, in a series of genotypic and phenotypic assays to determine differences that may influence transmission fitness. Methods: We analyzed the genetic diversity by next generation sequencing of acute/early HIV-1 isolated from the female genital tract and compared it to the diversity of HIV-1 in blood of the same patients. We then engineered chimeric viruses from acute and chronic envelope genes and evaluated them for host cell entry efficiency and kinetics, receptor affinity, replication fitness, sensitivity to entry inhibitors and transmission using ex vivo human mucosal explant tissue. Results: Genetic analysis revealed that acute/early HIV-1 isolates from blood are homogeneous while HIV-1 in the female genital tract showed high diversity. Furthermore acute isolates from the female genital tract displayed higher envelope glycosylation compared to HIV-1 from blood. We observed that both, acute and chronic HIV-1 isolates had similar entry kinetics, sensitivity to entry inhibitors and replicative fitness in primary cells. In contrast the evaluation of acute and chronic HIV-1 in human cervical and penile tissue clearly demonstrated that acute virions penetrate tissue, bind to residing DCs and establish infection of T cells more efficiently than chronic HIV-1, which were trapped and replicated in tissue. Higher transmission fitness of acute HIV correlated with reduced envelope N-linked glycosylation resulting in reduced lectin binding affinity. Conclusions: Mucosal tissues, the major sites of heterosexual HIV transmission have high levels of extracellular soluble lectins and C-type lectins expressed on epithelial cells which are designed to prevent infection of high mannose-containing pathogens. As such, HIV-1 with reduced N-linked glycans may be passively selected for transmission by escaping the “lectin-trap”. 216 Selection of HIV Env Mutants With Altered Trimers by EMPIRIC Saturation Mutagenesis

Maria Duenas-Decamp ; Li Jiang; Dan Bolon; Paul R. Clapham University of Massachusetts Medical School, Worcester, MA, US

Background: HIV-1 vaccines need to elicit neutralizing antibodies (nabs) that target conserved Env epitopes to protect against diverse HIV-1. To achieve this, we need to increase our knowledge on how different amino acids affect Env trimer structure. Native Env trimers are likely to be closed to protect against nabs and only triggered to open by CD4. Our hypothesis is that tightly closed trimers will (1) hide immunodominant non-neutralizing or strain specific Env sites e.g. V3 loop, and (2) expose conserved epitopes e.g. on the trimer association domain. To identify Env residues that maintain a closed trimer, we used EMPIRIC (Exceedingly Meticulous and Parallel Investigation of Randomized Individual

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CROI 2015