ALV-J strain SCAU-HN06 induces innate immune responses in chicken primary monocyte-derived macrophages

Abstract

Avian leucosis virus subgroup J (ALV-J) can cause lifelong infection and can escape from the host immune defenses in chickens. Since macrophages act as the important defense line against invading pathogens in host innate immunity, we investigated the function and innate immune responses of chicken primary monocyte-derived macrophages (MDM) after ALV-J infection in this study. Our results indicated that ALV-J was stably maintained in MDM cells but that the viral growth rate was significantly lower than that in DF-1 cells. We also found that ALV-J infection significantly increased nitric oxide (NO) production, but had no effect on MDM phagocytic capacity. Interestingly, infection with ALV-J rapidly promoted the expression levels of Myxovirus resistance 1 (Mx) (3 h, 6 h), ISG12 (6 h), and interleukin-1β (IL-1β) (3 h, 12 h) at an early infection stage, whereas it sharply decreased the expression of Mx (24 h, 36 h), ISG12 (36 h), and made little change on IL-1β (24 h, 36 h) production at a late infection stage in MDM cells. Moreover, the protein levels of interferon-β (IFN-β) and interleukin-6 (IL-6) had sharply increased in infected MDM cells from 3 to 36 h post infection (hpi) of ALV-J. And, the protein level of interleukin-10 (IL-10) was dramatically decreased at 36 hpi in MDM cells infected with ALV-J. These results demonstrate that ALV-J can induce host innate immune responses and we hypothesize that macrophages play an important role in host innate immune attack and ALV-J immune escape.

Molecular cloning and transcriptional regulation of Indian peafowl (Pavo cristatus) IFN-α gene

“…As type I IFNs, IFN-α firstly binds with specific transmembrane receptors and exhibits antiviral activity by stimulating various downstream ISG expression (Schneider et al 2014). At an early stage of viral infection in chicken, a number of ISGs, including the Mx1 and ISG12, were induced (Feng et al 2017) to inhibit virus release or protein lysis, thus enhancing innate immune signaling and antiviral functions . As one of the first depicted inhibitors of virus invasion, the Mx1 gene product broadly inhibits genome replication at an early post-entry step of the virus life cycle (Schneider et al 2014).…”

Immunity to Avian Leukosis Virus: Where Are We Now and What Should We Do?

“…Recently, we determined that chicken primary monocyte-derived macrophages (MDM) were susceptible to ALV-J (40). ALV-J strain SCAU-HN06 (41) rapidly increased the expression of Mx, ISG12-1 , IL-1β, IL-6, and IFN-β in MDM at early infection stages, but Mx, ISG12-1 , and IL-10 expression decreased sharply at 36 h postinfection (40).…”

“…ALV-J strain SCAU-HN06 (41) rapidly increased the expression of Mx, ISG12-1 , IL-1β, IL-6, and IFN-β in MDM at early infection stages, but Mx, ISG12-1 , and IL-10 expression decreased sharply at 36 h postinfection (40). This result indicated that ALV-J most likely escaped the innate immune response in chicken macrophages.…”

“…Chicken macrophages and DCs can be directly infected by ALV and induce innate immunity (40, 44). However, we still have no clear knowledge of the regulation of the global innate immune response to ALV infection and ALV evasion of the host innate immune response.…”

ALV-J infection induces chicken monocyte death accompanied with the production of IL-1β and IL-18

“…ALV subgroup J (ALV-J) infections greatly enhance the probability of a secondary infection through virally-induced immunosuppression. Our previous studies demonstrated that ALV-J induces host innate immune responses in chicken’s primary monocyte-derived macrophages suggesting that macrophages are important in ALV-J associated immune defense and escape [ 4 ]. ALV-J infection also inhibits differentiation and maturation of chicken bone marrow-derived dendritic cells (BM-DC) and triggers their apoptosis [ 5 , 6 ].…”