Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

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The majority of freshly sorted SIV-specific CD8 + T cells cannot suppress viral replication in SIV-infected macrophages Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison Madison, WI, USA

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The majority of freshly sorted SIV-specific CD8 + T cells cannot suppress viral replication in SIV-infected macrophages. Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison Madison, WI, USA. Evidence of HIV/SIV infection of macrophages. - PowerPoint PPT Presentation

Transcript of Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Page 1: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

The majority of freshly sorted SIV-specific CD8+ T cells cannot suppress viral replication in SIV-

infected macrophagesLara Vojnov, PhD

Department of Pathology and Laboratory MedicineUniversity of Wisconsin-Madison

Madison, WI, USA

Page 2: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Evidence of HIV/SIV infection of macrophages

Zhang et al. Science 1999

Veazey et al. Science 1998

In vivo SIVmac239 infection of macrophages in intestinal

lymphoid nodule

CD68+ macrophages comprise 10% of the

SIVmac251 cell population in vivo

Page 3: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Evidence of HIV/SIV infection of macrophages

Zhang et al. Science 1999

Veazey et al. Science 1998

PNAS 2001

Page 4: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

SAMHD1 inhibits HIV infection of macrophages without Vpx

Page 5: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Hypothesis

Macrophages play an important role in HIV/SIV infection as a

viral reservoir resistant to CTL-mediated lysis.

Page 6: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

SIV-specific CD8+ T cells suppress viral replication in SIV-infected CD4+ T cells

MHC matchedinfected targets

MHC mismatchedinfected targets

Page 7: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

SIV-specific CD8+ T cells poorly suppress viral replication in SIV-infected macrophages

MHC matchedinfected targets

MHC mismatchedinfected targets

Page 8: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

CD4+ T cells vs macrophages

Page 9: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

SIV-specific CD8+ T cells poorly suppress viral replication in SIV-infected macrophages

32% 88%

Page 10: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

SIV-specific CD8+ T cells poorly suppress viral replication in SIV-infected macrophages

3% 30%

Page 11: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Bulk CD8+ T cells suppress viral replication in SIV-infected CD4+ T cells

Page 12: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Bulk CD8+ T cells poorly suppress viral replication in SIV-infected macrophages

Page 13: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

Time-course of SIV-infected elite controllers

Page 14: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison

AcknowledgementsNational Institutes of Health

Jorge AlmeidaDanny Douek

NEPRCR. Paul Johnson

FIOCRUZ – Rio De JaneiroMyrna Bonaldo

Marlon Veloso de SantanaPatricia Costa Neves

Ricardo Galler

University of Wisconsin-MadisonMauricio MartinsAlexander Bean

Jonah SachaHolly Kolar

Nancy WilsonBenjamin BurwitzDavid O’Connor

University of MiamiDavid WatkinsAnn Dauphin

Mario Stevenson

Page 15: Lara Vojnov, PhD Department of Pathology and Laboratory Medicine University of Wisconsin-Madison