NDLI: Initial HIV-1 Antigen-Specific CD8+ T Cells in Acute HIV-1 Infection Inhibit Transmitted/Founder Virus Replication

Content Provider	PubMed Central
Author	Freel, Stephanie A. Picking, Ralph A. Ferrari, Guido Ding, Haitao Ochsenbauer, Christina Kappes, John C. Kirchherr, Jennifer L. Soderberg, Kelly A. Weinhold, Kent J. Cunningham, Coleen K. Denny, Thomas N. Crump, John A. Cohen, Myron S. Mcmichael, Andrew J. Haynes, Barton F. Tomaras, Georgia D.
Copyright Year	2012
Abstract	CD8-mediated virus inhibition can be detected in HIV-1-positive subjects who naturally control virus replication. Characterizing the inhibitory function of CD8+ T cells during acute HIV-1 infection (AHI) can elucidate the nature of the CD8+ responses that can be rapidly elicited and that contribute to virus control. We examined the timing and HIV-1 antigen specificity of antiviral CD8+ T cells during AHI. Autologous and heterologous CD8+ T cell antiviral functions were assessed longitudinally during AHI in five donors from the CHAVI 001 cohort using a CD8+ T cell-mediated virus inhibition assay (CD8 VIA) and transmitted/founder (T/F) viruses. Potent CD8+ antiviral responses against heterologous T/F viruses appeared during AHI at the first time point sampled in each of the 5 donors (Fiebig stages 1/2 to 5). Inhibition of an autologous T/F virus was durable to 48 weeks; however, inhibition of heterologous responses declined concurrent with the resolution of viremia. HIV-1 viruses from 6 months postinfection were more resistant to CD8+-mediated virus inhibition than cognate T/F viruses, demonstrating that the virus escapes early from CD8+ T cell-mediated inhibition of virus replication. CD8+ T cell antigen-specific subsets mediated inhibition of T/F virus replication via soluble components, and these soluble responses were stimulated by peptide pools that include epitopes that were shown to drive HIV-1 escape during AHI. These data provide insights into the mechanisms of CD8-mediated virus inhibition and suggest that functional analyses will be important for determining whether similar antigen-specific virus inhibition can be induced by T cell-directed vaccine strategies.
Related Links	http://dx.doi.org/10.1128/jvi.00437-12
Ending Page	6846
Page Count	12
Starting Page	6835
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	12
Volume Number	86
Language	English
Publisher	American Society for Microbiology
Publisher Date	2012-06-15
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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