Abstract
Natural killer (NK) cells may be important in modulating HIV replication in early course of HIV infection. The effector function of NK cells is finely tuned by a balance between signals delivered by activating and inhibitory receptors. However, the influence of expression of these receptors on the early course of HIV replication and subsequent disease progression is not explored in the context of HIV-1C infection. The expression pattern of activating (NKp46, NKp44, NKp30, NKG2D, and NKG2C) and inhibitory (CD158b, NKG2A, and ILT2) receptors was determined in 20 patients with recent HIV-1C infection within 3–7 months of acquiring HIV infection and was compared with the expression pattern in individuals with progressive (N = 12), non-progressive HIV-1C infection (LTNPs, N = 12) and healthy seronegative individuals (N = 20). The association of the expression of these receptors on the rate of disease progression was assessed using viral load set point of recently infected individuals as a marker of disease progression. The study showed that higher cytotoxic potency of NK cells was associated with low viral load set point in recent HIV infection (r = −0.701; p = 0.0006) and higher CD4 counts (r = 0.720; p = 0.001). The expression of activating receptors (NKp46, NKp30, and NKG2D) on cytotoxic NK cells but not on regulatory NK cells was also significantly associated with low viral set point (p < 0.01) and viral load in LTNPs and progressors (p < 0.01). The study also indicated that cytotoxic NK cells might show the ability to specifically lyse HIV infected CD4 cells. This data collectively showed that early and sustained higher expression of activating receptors on cytotoxic NK cells could be responsible for increased cytotoxicity, reduced viral burden, and thus delaying the disease progression. The study to identify the molecular mechanism of the expression of these receptors in HIV infection will be helpful in further understanding of NK cell mediated control in early HIV infection.
Highlights
HIV infection is characterized by a dynamic interaction between the host immune system and the virus
Natural killer (NK) cell frequency in patients with recent HIV infection (RHI) having high viral load set point (RHI-HVL) was found to be significantly lower as compared to RHI-LVL group (p = 0.011) and but similar with the NK cells frequency seen in progressors (p = 0.16) (Figure 3A)
NK CELL SUBSETS IN RECENT HIV INFECTION Cytotoxic NK cells (CD3−CD56+CD16+) is a major NK cell subset responsible for cytolysis of virally infected cells
Summary
HIV infection is characterized by a dynamic interaction between the host immune system and the virus. The important role of innate immune responses in early consequences of HIV infection has been highlighted recently [1, 2]. Increased NK cell activation has been associated with resistance to HIV-1 infection in a cohort of intra-venous drug users [6], HIV-discordant couples [7], and perinatally exposed children born to HIV-1 infected mothers [8]. These studies suggest that early NK cell response to HIV might be important in early control over virus multiplication. A recent RV144 HIV-1 vaccine efficacy trial demonstrated that plasma IgG against the HIV-1 envelope (env) variable region 1 and 2 inversely correlated with risk probably due to their ability to promote ADCC further emphasizing probable protective role of NK cells in HIV-1 infection [9]
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