Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated control

Rutger Luteijn, Gaia Sciaranghella, Jan van Lunzen, Anne Nolting, Anne-Sophie Dugast, Musie S Ghebremichael, Marcus Altfeld, Galit Alter

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR(+) NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR(+) NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK-cell-mediated innate pressure.

Original languageEnglish
Pages (from-to)2729-40
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number9
DOIs
Publication statusPublished - Sept 2011
Externally publishedYes

Keywords

  • Adult
  • Aged
  • CX3C Chemokine Receptor 1
  • Cell Movement/immunology
  • Cells, Cultured
  • Gene Expression Regulation/immunology
  • HIV/pathogenicity
  • HIV Infections/immunology
  • Humans
  • Immune Evasion
  • Immunity, Innate
  • Killer Cells, Natural/immunology
  • Lymph Nodes/pathology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Receptors, Chemokine/genetics
  • Receptors, Interleukin-8A/genetics
  • Receptors, KIR/genetics
  • TNF-Related Apoptosis-Inducing Ligand/genetics
  • Virus Replication

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