Antiviral NK cell responses in HIV infection: II. viral strategies for evasion and lessons for immunotherapy and vaccination

Abstract

As is the case in other viral infections, humans respond to HIV infection by activating their NK cells. However, the virus uses several strategies to neutralize and evade the host's NK cell responses. Consequently, it is not surprising that NK cell functions become compromised in HIV-infected individuals in early stages of the infection. The compromised NK cell functions also adversely affect several aspects of the host's antiviral adaptive immune responses. Researchers have made significant progress in understanding how HIV counters NK cell responses of the host. This knowledge has opened new avenues for immunotherapy and vaccination against this infection. In the first part of this review article, we gave an overview of our current knowledge of NK cell biology and discussed how the genes encoding NK cell receptors and their ligands determine innate genetic resistance/susceptibilty of humans against HIV infections and AIDS. In this second part, we discuss NK cell responses, viral strategies to counter these responses, and finally, their implications for anti-HIV immunotherapy and vaccination.

Human Pluripotent Stem Cells Produce Natural Killer Cells That Mediate Anti-HIV-1 Activity by Utilizing Diverse Cellular Mechanisms

“…5A; as a representative of CCL4, others are not shown). In addition, NK cell-produced cytokines, such as IFN-␥, can mediate anti-HIV activity via noncytolytic mechanisms (27). The results shown in Fig.…”

HIV Infection Abrogates the Functional Advantage of Natural Killer Cells Educated through KIR3DL1/HLA-Bw4 Interactions To Mediate Anti-HIV Antibody-Dependent Cellular Cytotoxicity

“…As HIV-infected individuals often carry antilymphocyte Abs (4) and potentially demonstrate soluble gp120 binding to uninfected CD4 ϩ T lymphocytes (16), future research needs to evaluate whether 3DL1-educated NK cells are functional in these potentially pathological situations. It is essential to establish which educated NK cell-mediated effector functions are truly beneficial and which are potentially pathogenic before such effector functions can be targeted as therapies and/or vaccines to HIV-infected individuals or individuals at risk.…”

Role of Natural Killer Cells in a Cohort of Elite Suppressors: Low Frequency of the Protective KIR3DS1 Allele and Limited Inhibition of Human Immunodeficiency Virus Type 1 Replication In Vitro

“…NK cells of patients with chronic HIV-1 have altered phenotypes and effector capabilities: NK cells from viremic patients have an increased expression of inhibitory receptors, and there is an expansion of the defective CD56 Ϫ NK cells compared to the levels in patients on highly active antiretroviral therapy or in ES (7,27). These changes may be due to alterations in the cytokine environment during infection, which can affect the activation of the NK cells (39); they also may be due to direct interactions between HIV-1 gene products and the NK cells (20). Although the precise cause is unknown, the result is the development of defective NK cells that express an altered receptor and NK cell marker phenotype.…”