lactoferrin and Respiratory-Syncytial-Virus-Infections

Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clinical disease in an in vivo murine model.. Female BALB/c mice were inoculated with 10(7)PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until 96h post-RSV inoculation. Bronchoalveolar lavage (BAL), whole lung and serum samples were harvested on day 5 post-inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups.. On day 5 post-inoculation BAL RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV infected but untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1-5 post-inoculation which was comparable to infected untreated mice (p>0.05) but higher than uninfected controls.. Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk for RSV infection needs to be further explored.

Topics: Animals; Anti-Infective Agents; Antiviral Agents; Bronchoalveolar Lavage Fluid; Cytokines; Disease Models, Animal; Female; Lactoferrin; Lung; Mice; Mice, Inbred BALB C; Pneumonia; Respiratory Function Tests; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Viral Load; Virus Replication

Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but down-regulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F(1) subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F(2) subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

Topics: Cell Line; Hemolysis; Humans; Interleukin-8; Lactoferrin; Pulmonary Surfactant-Associated Protein A; Respiratory Syncytial Virus Infections; Viral Proteins