{"id":23729,"date":"2020-04-29T13:24:44","date_gmt":"2020-04-29T08:54:44","guid":{"rendered":"http:\/\/hafshejan.webexir.net\/veterinary\/?p=23729"},"modified":"2020-07-14T11:32:14","modified_gmt":"2020-07-14T07:02:14","slug":"porcine-sialoadhesin-suppresses-type-i-interferon-production-to-support-porcine-reproductive-and-respiratory-syndrome-virus-infection","status":"publish","type":"post","link":"https:\/\/fa.hafshejan-co.com\/veterinary\/porcine-sialoadhesin-suppresses-type-i-interferon-production-to-support-porcine-reproductive-and-respiratory-syndrome-virus-infection\/","title":{"rendered":"Porcine sialoadhesin suppresses type I interferon production to support porcine reproductive and respiratory syndrome virus infection"},"content":{"rendered":"\n<p style=\"text-align: justify;\"><strong>Abstract<\/strong><br \/>Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant threat to the global swine industry. Porcine sialoadhesin (poSn) has been previously shown to mediate PRRSV attachment and internalization. In the current study, we report its unidentified role in antagonism of type I interferon (IFN) production during PRRSV infection. We determined that poSn facilitated PRRSV infection via inhibition of type I IFN transcription. Mechanistically, poSn interacted with a 12 kDa DNAX-activation protein (DAP12), which was dependent on residues 51\u201357 within DAP12 transmembrane domain (TMD). PRRSV exploited the poSn-DAP12 pathway to attenuate activation of nuclear factor-kappa B (NF-\u03baB). More importantly, the poSn-DAP12 pathway was involved in inhibiting poly (I:C)-triggered IFN production. All these results reveal a novel role of poSn in suppressing host antiviral responses, which deepens our understanding of PRRSV pathogenesis.<\/p>\n<p style=\"text-align: justify;\"><strong>Introduction<\/strong><br \/>Porcine reproductive and respiratory syndrome (PRRS) has been causing significant economic losses to the global swine industry [1]. Its clinical signs are respiratory distress and reproductive failure [2]. PRRS virus (PRRSV), as the causative agent, belongs to the Porarterivirus genus, Arteriviridae family in the order Nidovirales [3]. It is a single-stranded positive RNA virus with a genome of 14.9 to 15.5 kb in length. All PRRSV isolates are classified into PRRSV-1 and PRRSV-2, and PRRSV-2 strains are predominantly prevalent in China [4].<\/p>\n<p style=\"text-align: justify;\">Porcine sialoadhesin (poSn) was first identified to be involved in PRRSV entry [5]. Subsequent research indicated that poSn is responsible for virus attachment and internalization, which is dependent on the sialic acid-binding activity of its N-terminal immunoglobulin (Ig)-like domain [6,7,8]. Non-permissive cells with co-expression of recombinant poSn and CD163 produce much more viral progenies than that expressing CD163 alone [9]. However, a recent report demonstrated that poSn knockout pigs are still susceptible to PRRSV [10]. These studies suggested that poSn might play certain unappreciated roles instead of an indispensable receptor during PRRSV infection.<\/p>\n<p style=\"text-align: justify;\">poSn is a member of the sialic acid-binding Ig-like lectin (Siglec) family, namely Siglec-1 [11, 12]. Increasing evidence has shown that Siglecs modulate type I interferon (IFN) responses during viral infections. For example, Siglec-G is reported to be induced and exploited by RNA viruses to inhibit retinoic acid-inducible gene-I (RIG-I)-mediated type I IFN production [13]. Siglec-H is demonstrated to negatively regulate IFN-\u03b1 production in response to murine cytomegalovirus infection in vitro and in vivo [14]. Murine Siglec-1 has been recently shown to inhibit IFN responses through impairing tank binding kinase 1 (TBK1)-interferon regulatory factor (IRF)-3 pathway during vesicular stomatitis virus (VSV) infection [15]. As a Siglec, whether poSn plays an immunosuppressive role during PRRSV infection has not been elucidated.<\/p>\n<p style=\"text-align: justify;\">In this work, we unraveled that PRRSV utilized poSn to repress type I IFN production in favor of its infection. poSn associated with DNAX-activation protein of 12 kDa (DAP12) to attenuate PRRSV-triggered nuclear factor-kappa B (NF-\u03baB) activation. More importantly, poSn-DAP12 pathway negatively modulated transcription of type I IFNs in response to poly (I:C), suggesting that the pathway might be involved in maintaining homeostasis by avoiding excessive immune responses.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>AbstractPorcine reproductive and respiratory syndrome virus (PRRSV) is a significant threat to the global swine industry. Porcine sialoadhesin (poSn) has been previously shown to mediate PRRSV attachment and internalization. In the current study, we report its unidentified role in antagonism of type I interferon (IFN) production during PRRSV infection. We determined that poSn facilitated PRRSV&hellip;<\/p>\n","protected":false},"author":3,"featured_media":23735,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[53,35],"tags":[],"class_list":["post-23729","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-livestock","category-articles"],"acf":[],"_links":{"self":[{"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/posts\/23729","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/comments?post=23729"}],"version-history":[{"count":0,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/posts\/23729\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/media\/23735"}],"wp:attachment":[{"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/media?parent=23729"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/categories?post=23729"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fa.hafshejan-co.com\/veterinary\/wp-json\/wp\/v2\/tags?post=23729"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}