Natural Killer Cell Infection By HIV-1

Natural Killer Cell Infection By HIV-1

Identification of a new important HIV reservoir in NK cells

We identified a subset of CD56+CD16+CD3- natural killer (NK) cells in healthy donors that express CD4 and the HIV coreceptors CCR5 and CXCR4. These cells are also found in the peripheral blood of HIV infected individuals and can be productively infected by both CCR5 and CXCR4-using clones of HIV-1. Similar to the case in T-cells, CD4 is required for infection.

Analysis of samples from HIV infected persons showed that viral DNA is present in purified NK cells and virus could be rescued from these cells after in vitro cultivation. Therefore, these cells are part of the permanent virus reservoir in vivo. To control virus replication and AIDS development, virus propagation in these cells needs to be addressed.

Infection of these important innate immune cells by HIV may be relevant for the defects in innate immunity observed in AIDS patients.

Read the NCI press release

Go to PNAS in press: Natural Killer cells are HIV-1 infected in vivo

Simple facts about HIV infection of Natural Killer cells

Phenotypic Analysis of CD4+ NK cells

CD3-CD56+CD4+

CD16+

CCR5+, CXCR4+

TCRab-, TCRgd-

CD14-, CD19-, CD80-, CD86-

CD2+

KIR+ (NKAT2, CD158a, CD94)

CD25-, IL-2Rb-

Conclusions-NK Infection

A non-T non-monocyte leukocyte subset having NK markers is infected by HIV in vitro and in vivo (CD3-CD56+CD16+CD4+)

The receptors for HIV-1 CD4, CCR5 and CXCR4 are expressed in a subset of human natural killer cells

Infection of NK cells is productive and requires CD4 and HIV coreceptors CCR5 or CXCR4

NK cells are persistently infected in vivo even in patients under HAART

NK cells of HAART patients harbor infectious virus

The distribution of Innate Immunity effector cells changes in HIV+ persons compared to normal volunteers (unpublished data). NK cells is one type of innate immunity effectors.

The newly identified CD4+NK subpopulation may be important for understanding NK biology and the role of NK and innate immune system in HIV infection

Antonio Valentin

Margherita Rosati

Dan Patenaude

George N. Pavlakis

Human Retrovirus Section

Basic Research Laboratory

Natl. Cancer Institute-Frederick