Soluble factors from T cells inhibiting X4 strains of HIV are a mixture of β chemokines and RNases

Abstract

T-cell-derived soluble factors that inhibit both X4 and R5 HIV are recognized as important in controlling HIV. Whereas three β chemokines, regulated-on-activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β, account for the suppression of R5 HIV by blockade of HIV entry, the major components responsible for the inhibition of X4 HIV strains have not been identified previously. We identify these factors primarily as a mixture of three β chemokines [macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), and I-309] and two RNases (angiogenin and RNase 4) of lesser potency and show that in a clade B population, some correlate with clinical status and are produced by both CD4 + and CD8 + T cells (chemokines, angiogenin) or only by CD8 + T cells (RNase 4). The antiviral mechanisms of these HIV X4-suppressive factors differ from those of the previously described HIV R5-suppressive β chemokines.

Human T h 17 Cells Lack HIV-Inhibitory RNases and Are Highly Permissive to Productive HIV Infection

“…Of the eight human RNase proteins that have been functionally characterized, four had already been shown to have HIV-inhibitory activity (63). The secretion of RNase 4 and RNase 5/angiogenin by T cells was recently identified as a mechanism of HIV inhibition (64). Recombinant human RNase 1, RNase 2, and RNase 5 each inhibit the HIV infection of primary human T cells in vitro, whether added before or after infection.…”

Three decades of research on angiogenin: a review and perspective

“…In addition to antibacterial activities, ANG also has antiviral activities. As one of the two RNases produced by primary T cells, ANG can suppress the replication of the X4 HIV strains [116]. ANG-mediated tiRNAs are also increased and abundant in chronic hepatitis B and C infection, suggesting that ANG may play roles in viral infection [117].…”

Antiviral activities of whey proteins

“…Usually, the antiviral mechanisms of the milk proteins and antiviral agents are distinctly different, and they inhibited different steps in the viral replication cycle (van der Strate et al 2003). Lactoferrin has antimicrobial properties against bacteria, fungi, and several viruses (Neurath et al 1995;Berkhout et al 1997) Bovine lactoferrin and lactoferricin blocks viral entry into host cells and CXCR4 or CCR5 attachment (Berkhout et al 2002) Bovine lactoferrin in apo-form or forms saturated with ferric, manganese or zinc ions suppresses HIV-1 replication and syncytium formation, inhibits viral binding and entry into host cells (Puddu et al 1998) Secretory leukocyte protease inhibitor inhibits HIV-1 replication (Farquhar et al 2002) Peptides composed of residues 98-115 and107-115 of human lysozyme disrupts viral particle, prevents its binding and entry into target cells (Lee-Huang et al 2005) Angiogenin inhibits HIV-1 replication (Bedoya et al 2006;Cocchi et al 2012) Milk mucin inhibits HIV-1 infectionby physically aggregation with the virus through a charge interaction with its negatively charged carbohydrate side chains containing highsialic acid and sulphate content (Habte et al 2008;Mthembu et al 2014) tenascin-C neutralizes HIV-1 by binding the viral envelope protein at the chemokine coreceptor site CD4 (Fouda et al 2013) Human cytomegalovirus…”

“…This is because MUC1 in crude milk is surrounded by fat globules, and to act against the virus, it has to be liberated from the fat globules (Habte et al 2008). Angiogenin is a milk protein with both ribonuclease and anti-HIV activities (Bedoya et al 2006;Cocchi et al 2012).…”