Sib txawv tab sis tsis txawv: Deciphering Immunity ntawm Jamaican Txiv Hmab Txiv Ntoo Bat Los ntawm Kev Kawm Nws Viriome
Mar 06, 2023
Abstract:
Ib qho tshwj xeeb thiab zoo-tuned tiv thaiv kab mob ntawm cov puav thaum kis kab mob yog ntseeg tau muab lub hauv paus rau "phooj ywg" kev sib raug zoo nrog cov kab mob no, uas feem ntau ua rau tib neeg thiab lwm yam tsiaj. Thawj qhov kev nkag siab rau hauvtiv thaiv kab mobntawm puav qhia tias puav tau hloov zuj zus los muaj lawv cov tswv yim los tiv thaiv kab mob. Txawm li cas los xij, cov ntsiab lus molecular rau qhov kev sib koom ua ke tsis zoo no tseem piav qhia tsis zoo thiab cov qauv kab mob puav yog tus yuam sij rau kev nthuav tawm cov lus zais no. Hauv Jamaican txiv hmab txiv ntoo puav (Artibeus jamaicensis), ib hom kab mob tshiab ntiaj teb, kev sim kis nrog nws (putative) natural viral pathogens Tacaribe virus (TCRV), rabies virus (RABV), thiab bat influenza A virus (IAV) H18N11 tau pab txhawb. qhov tseeb, txawm tias tseem tsis tiav, sawv cev ntawm kev tiv thaiv kab mob bat. Kuj ceeb tias, txawm hais tias muaj ntau yam ntawm lawv qhov kev tiv thaiv kab mob hauv lub cev thiab hloov pauv lub cev tsis sib txawv ntawm tib neeg lub cev tiv thaiv kab mob, xws li kev cog lus ntawm IFN locus thiab txo qis ntawm cov immunoglobulin subclasses, kev hloov pauv kuj tuaj yeem pom ntawm Jamaican txiv hmab txiv ntoo puav thiab lwm yam puav. hom.
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1. Taw qhia
Lub Jamaican txiv hmab txiv ntoo-noj puav, Artibeus jamaicensis, yog ib hom tsiaj frugivorous uas yog nyob rau Central America. Nws qhov chaw nyob tseem ceeb yog cov hav zoov uas txuas los ntawm Southern Mexico thoob plaws hauv Caribbean thiab sab qaum teb thaj tsam ntawm South America, tab sis lawv nyob hauv ntau qhov siab ntawm subalpine mus rau qib dej hiav txwv [1,2]. Jamaican txiv hmab txiv ntoo puav tuaj yeem ncav cuag qhov hnyav txog li 60 g, nrog lub wingspan ntawm 96-150 mm; lawv tuaj yeem nyob txog kaum xyoo thiab yug ob zaug hauv ib xyoos, feem ntau yug tsuas yog ib tus menyuam dev [1,2]. Zoo li tag nrho lwm cov puav, lawv muaj cov metabolism hauv siab heev rau lawv qhov loj me uas yuav tsum tau noj cov calories tas li [3]. Cov yam ntxwv ntawm cov puav no yog lawv lub qhov ntswg-nplooj, lub ntsej muag lub cev uas yog siv rau echolocation, nrog rau kev sib txuas lus, foraging, thiab nrhiav tau ntawm predators. Raws li cov txiv hmab txiv ntoo noj puav, lawv cov khoom noj muaj feem ntau ntawm Ficus spp. figs, txawm hais tias lawv yuav qee zaus mus noj paj thiab kab yog tias cov txiv hmab txiv ntoo tsis muaj [2,4]. Yog li ntawd, cov puav no yog cov tseem ceeb pab rau cov noob dispersal, pollination, thiab tshuaj tua kab nyob rau hauv lawv ib puag ncig. Tsis tas li ntawd, lawv sawv cev rau ib qho khoom noj tseem ceeb rau ntau yam tsiaj txhu, suav nrog owls, nab, thiab lwm yam puav [1].
Ntau qhov kev tshawb fawb txij li xyoo 1950 tau pom tias Jamaican txiv hmab txiv ntoo puav muaj lub luag haujlwm tseem ceeb hauv kab mob ecology ib yam nkaus. Lawv tau pom tias kis tau ntau yam kab mob hauv qhov xwm txheej, suav nrog tus kab mob dengue (DENV) [5–7], West Nile virus (WNV) [8], Zika virus (ZIKV) [8], alpha coronaviruses (-CoV) [ 9], chikungunya virus (CHIKV) [10], Tacaribe virus (TCRV) [11,12], thiab tus kab mob rabies (RABV) [13–16], ntau yam uas yog kab mob rau tib neeg. Txawm hais tias muaj kab mob nrog DENV, WNV, thiab ZIKV yog vim muaj cov xwm txheej epizootic, nws tuaj yeem pom tau tias cov txiv hmab txiv ntoo ntawm Jamaican tuaj yeem sawv cev rau lub pas dej rau RABV [15]. TCRV, uas tau raug cais tawm ntawm puav ntawm ob hom Artibeus, tsis kis mus rau lwm tus puav nyob rau hauv kev sim [17].
Nyob rau hauv sib piv, genomic sequences ntawm bat influenza A virus (bat IAV) subtype H18N11 tau kuaj pom nyob rau hauv ntau hom Artibeus thiab tus kab mob no, ntxiv mus, pom tau mus serially kis ntawm sim kis kab mob Jamaican txiv hmab txiv ntoo puav, raws li nws lub luag hauj lwm raws li ib tug putative reservoir hom. Kawm txog kev sib raug zoo ntawm cov kab mob no thiab lawv (putative) natural party, Jamaican txiv hmab txiv ntoo puav, tau tso qee qhov teeb meem ntawm cov txheej txheem ntawm yuav ua li cas cov puav no tuaj yeem tiv taus tus kab mob thiab zam cov tsos mob hnyav ntawm cov kab mob sib txawv rau cov neeg tuag xws li tib neeg. .
2. Kev tshawb fawb txog kab mob
2.1. Tacaribe Virus
TCRV yog tus kab mob arenavirus uas tau raug cais tawm thawj zaug hauv xyoo 1950, tshaj tawm los ntawm Jamaican txiv hmab txiv ntoo puav thiab cov txiv hmab txiv ntoo noj zoo (Artibeus lituratus) hauv Port-of-Spain, Trinidad [12]. Cov kev tshawb fawb tom qab siv cov cuab yeej molecular tau txiav txim siab tias Jamaican txiv hmab txiv ntoo puav tsis pom nyob rau hauv Trinidad, tab sis hloov, cov no feem ntau yog misidentified flat-faced txiv hmab txiv ntoo puav (Artibeus planirostris) [18]. Nyob rau hauv tag nrho, TCRV raug cais tawm ntawm 6 lub txiv hmab txiv ntoo zoo noj puav thiab tsib lub ntsej muag cov txiv hmab txiv ntoo hauv xyoo 1950, qhia txog kev nthuav dav ntawm cov kab mob no ntawm Artibeus spp. Txawm hais tias kev siv zog los khaws txhua kaum ib tus neeg nyob ib leeg, tsuas yog ib qho ntawm cov kab mob no tseem tshuav: TRVL-11573, uas tau cais tawm ntawm cov txiv hmab txiv ntoo zoo heev [19]. Cov tshuaj tiv thaiv rau TCRV kuj tau pom nyob rau hauv lwm cov txiv hmab txiv ntoo noj puav, xws li Seba's luv-tailed bat (Carollia perspicillata) thiab cov txiv hmab txiv ntoo daj-lub xub pwg (Sturnira Lilium) [11].
Tsis tas li ntawd, raws li TCRV tau txwv tsis pub tsuas yog cais tawm ntawm cov zuam nyob rau sab qaum teb Florida, Tebchaws Asmeskas (qhov twg cov puav txiv ntoo tsis pom) [20], nws xav tias tsuas yog New World arenavirus uas tsis paub cov pas dej nas [17].
Kev sim kab mob ntawm Jamaican txiv hmab txiv ntoo puav nrog ib koob tshuaj tsawg ntawm TCRV (104 TCID50), ob qho tib si subcutaneously lossis los ntawm txoj hauv kev intranasal, ua rau muaj qhov tsis zoo, kab mob apathogenic, thiab tshem tawm cov kab mob. Hauv qhov sib piv, cov koob tshuaj ntau ntawm tus kab mob (106 TCID50) tau muab tshuaj subcutaneously lossis intranasally ua rau muaj kab mob hauv lub paj hlwb (xws li, cov lus teb tsis zoo rau cov neeg kho tshuab stimuli thiab incoordination, nrog rau tis, pob ntseg, thiab lub taub hau tshee), tsis muaj peev xwm ya, thiab kev tuag siab. Txawm hais tias muaj tus qauv pom tseeb ntawm kev kis tus kab mob hauv cov kab mob uas muaj kab mob siab, TCRV-tshwj xeeb RNA thiab tus kab mob kis tau raug pom thawj zaug hauv tus po ua ntej lawv kuaj pom hauv ntau lwm yam kabmob, suav nrog lub ntsws, daim siab, hnyuv, thiab lub hlwb, qhov kawg ntawm qhov ntawd. tau tshwm sim tshwj xeeb nrog rau qhov tshwm sim tuag taus.
Kev tshawb fawb histopathological tau qhia tias cov puav tau raug mob los ntawm kev mob ntsws ua ke nrog cov ntaub so ntswg puas nyob hauv daim siab thiab tus po, nrog rau (feem ntau) qhov mob hauv lub hlwb [17]. Intriguingly, kab rov tav kev sim tau pom tias TCRV tsis muaj peev xwm kis tau ntawm cov inoculated pub bats thiab naïve hu rau tsiaj, ua rau kev xav tias Jamaican txiv hmab txiv ntoo puav yuav tsis yog lub ntuj reservoir hom ntawm TCRV [17]. Txawm li cas los xij, nws tseem yuav tau txiav txim siab li cas TCRV kis Artibeus puav nyob rau hauv qhov xwm txheej thiab yuav ua li cas nws ua tiav kev sib kis ntawm cov puav no.
Cov kev tshawb fawb tom qab ntawm tus po, daim siab, thiab ob lub raum ntawm cov kab mob Jamaican txiv hmab txiv ntoo puav tau qhia txog kev sib txawv ntawm lub cev hauv qhov induction ntawm innate thiab adaptive lub cev tiv thaiv kab mob [21]. Intriguingly, ntawm txoj kev tswj hwm qhov tseem ceeb tshaj plaws yog txoj kev cuam tshuam ntawm interferon (IFN)-kev taw qhia, uas feem ntau ntawm nws cov noob muaj feem xyuam (Ifit1, Ifit3, Ifi6, Irf9, Bax, Socs1, thiab Bcl2) tau raug tswj xyuas tsawg kawg ob ntawm peb. cov ntaub so ntswg tsom.
Tsis tas li ntawd, cov ntawv sau tseg rau hom II IFN, tab sis tsis yog hom I IFN, tau nce ntxiv ntawm kev tswj tsis tau kis. Tsis tas li ntawd, cov ntawv sau tseg rau cytokine (Il6, Il8, Il1a, thiab Il1b) thiab cov noob caj noob ces (Cxcl1, Cxcl2, Cxcl3, Cxcl5, thiab Cxcl6) tau nce siab. Kev nthuav qhia kos npe ntawm apoptosis, uas feem ntau cuam tshuam nrog kev ua haujlwm tiv thaiv kab mob, tau nce hauv lub raum, txawm hais tias txo qis hauv tus po thiab daim siab, raws li cov ntawv sau tseg rau cov cim anti-apoptotic BCL-2. Sera sau los ntawm cov kab mob siab thiab qis qis feem ntau tsis zoo rau cov tshuaj tiv thaiv kab mob.
Txawm li cas los xij, peb tus puav, uas TCRV-tshwj xeeb RNA tsis tau kuaj pom, kuaj pom zoo rau cov tshuaj tiv thaiv tsis zoo. Txawm hais tias muaj ntau qhov kev qhia ntawm cov ntawv sau npe rau cov immunoglobulin (Ig) isotypes IgM, IgE, IgA, thiab IgG hauv tus po, cov puav kab mob tsis pom muaj kev cuam tshuam ntawm cov noob koom nrog hauv somatic hypermutation thiab affinity maturation, uas tej zaum yuav suav rau cov tshuaj tiv thaiv qis. Raws li qhov xav tau, cov noob caj noob ces cuam tshuam nrog T thiab B lymphocyte kev ua haujlwm tau raug tswj hwm, tseem tsis tau muaj kev txhawb nqa hauv cov ntawv teev lus cuam tshuam nrog kev ua kom NK hlwb [21].
2.2. Rabies Virus
RABV yog ib hom kab mob rhabdovirus uas muaj nyob thoob plaws ntiaj teb hauv ntau hom tsiaj, tshwj xeeb tshaj yog txuam nrog canines thiab puav [22]. Kev kis mob ntawm tib neeg nrog RABV yog ze li ntawm ib txwm ua rau tuag taus, txawm tias muaj kev cuam tshuam [23]. Xyoo 1974, RABV raug cais tawm ntawm lub hlwb ntawm cov txiv hmab txiv ntoo tsis zoo ntawm Jamaican hauv La Tanta, Grenada [14]. Raws li nws muaj peev xwm kis tau rau ntau hom tsiaj, tus kab mob kis mus rau ntau lwm hom Artibeus, suav nrog cov txiv hmab txiv ntoo uas muaj ntsej muag thiab cov txiv hmab txiv ntoo zoo heev. Artibeus bat colonies nyob rau hauv Grenada yog li ntseeg tau tias yog reservoir ntawm RABV [13–16].
RABV yog tus kab mob tuag neurotropic, uas rov ua dua hauv lub hlwb thiab cov qog ua kua qaub. Cov qaub ncaug uas muaj kab mob nkag mus rau hauv lub cev intramuscularly los ntawm kev tom, khawb, lossis thaum tu, tom qab ntawd nws mus rau hauv nruab nrab lub paj hlwb [24]. Los ntawm qhov no, kev tshawb fawb yav dhau los siv tus nas-hloov RABV hom CVS-24 pom tias kev txhaj tshuaj intramuscular ntawm Jamaican txiv hmab txiv ntoo puav nrog cov kab mob siab (CVS-24-N2c) rau hauv txoj cai masseter leeg coj mus rau qhov dav. o nyob rau hauv lub hauv paus paj hlwb, yam ntxwv los ntawm lymphocyte infiltration, tshwj xeeb tshaj yog nyob rau hauv lub paj hlwb qia, leptomeningeal, thiab perivascular cheeb tsam. Txog hnub xya tom qab kis kab mob, puav kab mob CVS-24-N2c tsim ataxia, ceg paresis, thiab tsis muaj peev xwm ya tau, thaum cov puav tau kis tus kab mob qis qis CVS-24-B2c tsis pom cov tsos mob ntawm tus kab mob [25]. Nyob rau hauv sib piv rau cov kev soj ntsuam tau siv murine-derived CVS-24-N2c kab mob, intramuscular thiab subcutaneous kab mob ntawm intermediate txiv hmab txiv ntoo bat (Artibeus intermedius) nrog txawv vampire bat-derived RABVs tsis ua rau cov tsos mob ntawm tus kab mob thiab feem ntau ntawm cov puav sim kis kab mob seroconverted nrog neutralizing antibodies [26].
Txawm li cas los xij, cov kev tshawb fawb tshawb fawb txog txoj hauv kev ntawm kev sib kis tau tam sim no tsis muaj thiab, muab cov yam ntxwv tshwj xeeb ntawm lub hauv paus paj hlwb thiab nws lub cev tsis muaj zog [27], kev tshawb fawb txog kev tiv thaiv kab mob yog cuam tshuam [28].
Kev tshuaj xyuas serological tsis ntev los no uas tsom los txheeb xyuas qhov cuam tshuam ntawm cov puav rau RABV hauv Trinidad tau nthuav tawm cov puav txiv hmab txiv ntoo puag ncig, thaum lub sij hawm misidentified li Jamaican txiv hmab txiv ntoo puav, yog qhov seropositive tshaj plaws ntawm hom tshuaj ntsuam xyuas [15]. Interestingly, nws tshwm sim tias cov me nyuam mos puav leej muaj feem ntau yuav seropositive tshaj cov laus puav. Cov cheeb tsam hauv nroog kuj tseem muaj cov puav seropositive ntau dua li cov cheeb tsam nyob deb nroog.
Ntxiv mus, txawm tias muaj cov tshuaj tiv thaiv tsis zoo (titers xws li 10 txog 1900), cov puav no tsis pom cov tsos mob ntawm tus kab mob [15], qhia tias tsis zoo li cov kev sim kis kab mob uas siv cov murine CVS-24-N2c strain, tus kab mob. tsis yog tuag rau cov puav no. Cov kev tshawb fawb tau pom, tshwj xeeb tshaj yog, RABV hom kab mob ntawm cov kab mob hauv keeb kwm zoo li tsis tshua muaj kab mob hauv cov nas dua li cov kab mob los ntawm lwm lub pas dej, qhia txog kev hloov pauv ntawm tus kab mob rau nws tus tswv [29]. Raws li cov xwm txheej tau tshaj tawm ntawm kev sib kis ntawm cov puav thiab cov tsiaj nyeg ze rau Jamaican txiv hmab txiv ntoo bat thaj tsam, RABV ncig hauv cov puav no suav tias yog kev txhawj xeeb txog kev noj qab haus huv rau pej xeem hauv qee thaj tsam ntawm Grenada, txawm li cas los xij, nws cov kab mob sib piv rau RABV los ntawm lwm hom tseem tsis tau txiav txim siab. .
2.3. Bat Influenza A Virus H18N11
Hauv xyoo 2010, cov kab mob genome uas yog ib tus neeg tsis paub yav dhau los IAV ntawm H18N11 subtype raug cais tawm ntawm cov txiv hmab txiv ntoo uas muaj ntsej muag nyob hauv Peruvian Amazonia. Nyob rau xyoo tom ntej, H18N11 genome sequences kuj tau pom nyob rau hauv cov txiv hmab txiv ntoo tsaus nti (Artibeus obscurus) los ntawm Bolivia thiab cov txiv hmab txiv ntoo zoo heev los ntawm Brazil, qhia txog kev nthuav dav ntawm tus kab mob H18N11 ntawm Artibeus spp. [30].
Tom qab inoculation intranasal inoculation ntawm Jamaican txiv hmab txiv ntoo puav, ib tug zoo reservoir ntawm bat IAV [30], nrog 5 × 105 TCID50 ntawm H18N11, qee cov puav tau pom cov tsos mob me me ntawm cov kab mob, xws li qhov ntswg thiab qhov muag tawm. Txawm li cas los xij, tsis zoo li cov qauv IAVs (subtypes H1-16 thiab N1-9), uas feem ntau replicate nyob rau hauv lub epithelium ntawm cov kab mob ua pa, cov puav IAV H18N11 tsom rau squamous epithelium ntawm palatine tonsils, lamina propria ntawm cov hnyuv me, thiab cov follicle-associated epithelium ntawm jejunal Peyer thaj ua rau thaj. Histological staining ntawm cov kab mob plab hnyuv tau pom tus kab mob RNA hauv ob qho tib si enterocytes thiab cov tshuaj tiv thaiv kab mob (macrophages lossis dendritic cells). Nyob rau hauv txoj kab nrog kev soj ntsuam txoj hnyuv replication, cov puav kab mob tso cov quav uas muaj tus kab mob, uas ua rau muaj feem ntau yuav kis tau tus kab mob hauv qhov ncauj kab rov tav mus rau naïve hu bats [31]. Cov ntawv tshaj tawm yav dhau los ntawm cov txiv hmab txiv ntoo uas muaj lub ntsej muag lub ntsej muag thiab cov txiv hmab txiv ntoo noj cov puav zoo sib xws tau tshaj tawm txoj hnyuv rov ua dua thiab tso tawm ntawm H18N11 hauv qhov quav [30,32]. Lub peev xwm tsis muaj peev xwm ntawm tus puav IAV kom kis tau thiab rov ua dua hauv cov ntaub so ntswg lymphoid, uas yog nyob los ntawm ntau cov leukocytes, yog vim nws cov hemagglutinin nto glycoprotein H18, uas siv cov histocompatibility complex class II (MHC-II) proteins rau cell. chav kawm [33].
Nyob rau hauv cov ntsiab lus ntawm Jamaican txiv hmab txiv ntoo kab mob, cov neuraminidase protein N11, qhov thib ob nto glycoprotein ntawm tus puav IAV, tau tshwm sim yog qhov tseem ceeb rau kev kis tus kab mob. Cov kev sim tom qab hauv vitro tau qhia tias N11 tsis zoo tswj MHC-II qhia [31], xav tias yuav pab txhawb kev kis kab mob. Xav txog cov cellular tropism ntawm H18N11 hauv cov tshuaj tiv thaiv kab mob, cov tshuaj tiv thaiv kab mob hauv cov ntsiab lus ntawm CD4 ntxiv rau T hlwb yuav tsum tau hais.
Kev soj ntsuam serological ntawm cov puav ntes tau nyob rau hauv cheeb tsam Peruvian rainforest pom, thawj zaug, qhov feem ntawm cov puav seropositive yog siab tshaj ntawm Artibeus spp. thiab, qhov thib ob, muaj IgGs qhia rau H18 HA thiab N11 NA nto glycoproteins, nrog titers ntawm 1000 thiab, hauv qee cov puav, txawm tias 16,000 [30]. Raws li kev sim kab mob ntawm Jamaican txiv hmab txiv ntoo puav, Performance index thiab hu bats zoo sib xws seroconverted nrog antibodies rau tus kab mob nucleoprotein nrog titers ntawm 300-1000 (antibodies rau HA thiab NA tsis tau sim nyob rau hauv txoj kev tshawb no) [31].
3. Kev sib tham
Jamaican txiv hmab txiv ntoo puav yog ib tug dav faib thoob ntiaj teb bat hom uas qhia sib tshooj nyob nrog ntau lwm hom thiab, nce, tib neeg. Yog li ntawd, raws li tau hais los saum no, Jamaican txiv hmab txiv ntoo puav tau kis nrog ntau tus kab mob sib txawv hauv xwm [5,6,8,9,11,13,15,16,30]. Tsis tas li ntawd, nws tau raug siv los ua tus qauv kev sim kab mob rau ntau tus kab mob no, suav nrog cov txiv hmab txiv ntoo ntawm Jamaican ua ib lub chaw tso dej, xws li TCRV [17,21], RABV [25], thiab bat IAV H18N11 [31. ]. Cov kev sim kis kab mob no tau qhia txog qhov tshwj xeeb ntawm tus kab mob-tus tswv tsev sib koom ua ke thiab raug yuamtiv thaiv kab mob. Piv txwv li, cov kab mob TCRV tsawg, tab sis tsis yog kab mob siab, tso cai rau tus kab mob rov ua dua yam tsis muaj qhov pom tseeb pathology [17].
Txawm hais tias cov kab mob RABV ntuj ua rau tsis muaj qhov pom tseeb pathology, kev sim kab mob nrog tus nas-derived RABV strain ua rau mob hnyav [14-16]. Thaum kawg, kev sim kab mob ntawm cov puav nrog H18N11 ua rau feem ntau ntawm cov hnyuv replication, tsis muaj cov tsos mob ntawm tus kab mob me me, thiab kev kis mob fecal-qhov ncauj [31]. Ib cag ntawm cov kev tshawb fawb no, Jamaican txiv hmab txiv ntoo puav kuj tau siv rau kev sim kab mob nrog ZIKV [34], DENV [35,36], thiab Middle East respiratory syndrome coronavirus (MERS-CoV) [37]. Kev kis tus kab mob no tsis tau ua rau muaj tus kab mob txuas ntxiv (tshwj tsis yog MERS-CoV) lossis ua rau muaj kab mob. Txawm li cas los xij, cov txiaj ntsig ntawm cov kev tshawb fawb no, tshwj xeeb tshaj yog hais txog kev tiv thaiv kab mob, yuav tsum tau txhais nrog ceev faj, vim tias cov tshuaj tiv thaiv kab mob hauv cov kev sim no yuav tsis yog tus sawv cev ntawm tus tswv tsev hloov kho rau qee yam kab mob. Ntau dua li ua piv txwv ntawm tus kab mob-tus tswv tsev sib koom ua ke, cov kev sim kab mob epizootic no nquag tsim kom muaj kev tiv thaiv kab mob tsis sib haum raws li pom rau tib neeg tom qab kis kab mob zoonotic pathogens [38-43].
Txawm hais tias ua ntej, cov ntaub ntawv tam sim no muaj tso cai rau kos thawj cov lus xaus txog qhovtiv thaiv kab mobntawm Jamaican txiv hmab txiv ntoo puav thiab nws qhov sib txawv rau lwm hom puav, nrog rau tib neeg. Cov kev tshawb fawb sau tseg tau qhia tias Jamaican txiv hmab txiv ntoo bat encodes 466 lub cev tiv thaiv kab mob, sib xws rau 2 feem pua ntawm tag nrho cov ntawv sau tseg [44]. Ib yam li ntawd, qhov zoo-study Ntiaj Teb Dub ya hma liab (Pteropus alecto) thiab Egyptian txiv hmab txiv ntoo bat (Rousettus aegyptiacus) chaw nres nkoj 500 thiab 407 lub cev tiv thaiv kab mob sib txuas rau 3.5 feem pua thiab 2.75 feem pua, raws li, ntawm tag nrho [4 5,4 transcriptome]. . Hauv kev sib piv, tib neeg genome muaj 1562 cov kab mob tiv thaiv kab mob, suav nrog 7 feem pua ntawm tag nrho cov ntawv sau tseg [47]. Ib qho kev sib txawv ntawm kev tiv thaiv kab mob uas tau piav qhia rau cov hma liab ya dub yog kev cog lus ntawm hom I IFN locus [48]. Tsuas yog kaum hom tsis zoo kuv IFN noob tuaj yeem txheeb xyuas cov puav no, piv rau 16 paub rau tib neeg thiab 25 paub rau nas (Daim duab 1 A, B) [45,49]. Jamaican txiv hmab txiv ntoo puav tshwm sim ua raws li kev xav pom rau cov hma liab ya dub, txij li ntau hom kuv IFN pseudogenes (rau) raws li cov noob caj noob ces tau txheeb xyuas hauv nws cov genome, qhia txog kev hloov pauv ntawm hom kuv IFN loci. Txawm li cas los xij, qhov kev cog lus ntawm cov noob no yog qhov sib txawv ntawm qhov piav qhia nthuav dav ntawm hom I IFN noob tau txiav txim siab rau New World me me xim av puav (Myotis lucifugus), 28 cov noob, nrog rau Lub Ntiaj Teb Qub Hmab Loj (Pteropus vampyrus), 33 genes. , thiab Egyptian txiv hmab txiv ntoo bat, 46 noob [49,50]. Ib yam li lwm hom tsiaj, tsuas muaj ib hom II IFN (IFN-), uas tsis muaj kev sib raug zoo rau hom I IFN [51], hauv Jamaican txiv hmab txiv ntoo puav, hma dub ya, hma ya loj, cov txiv hmab txiv ntoo hauv Egypt, thiab me me xim av. cov puav. Txawm hais tias ob qho tib si ntawm hom III IFN receptor heterodimer, IFNLR1, thiab IL10R2, tau pom tias tau hais tawm hauv Jamaican txiv hmab txiv ntoo, ib hom kev ua haujlwm III IFN (IFN-λ) noob tseem tsis tau txheeb xyuas hauv NCBI genome database thiab Cov ntaub ntawv transcriptomic (Ntxiv daim duab S1).
Txawm li cas los xij, nws tsis tuaj yeem raug cais tawm tias qhov ua yuam kev hauv cov ntaub ntawv sib txuas ua rau muaj qhov tsis txaus ntseeg ntawm hom III interferon hauv Jamaican txiv hmab txiv ntoo puav. Yog tias nws tuav hom III IFN yog raug xaiv tsis zoo, nws yuav yog qhov sib piv rau cov hma dub ya, hma ya loj, me me xim av, thiab Egyptian txiv hmab txiv ntoo puav, uas tsawg kawg yog ib qho kev ua haujlwm gene encoding IFN-λ tau raug txheeb xyuas. (Daim duab 1C) [52,53]. Qhov tseem ceeb, IL10R2 kuj tsim cov heterodimeric receptor rau IL-10 thiab IL-22 [54], ob qho tib si tau hais hauv Jamaican txiv hmab txiv ntoo puav.
Txawm li cas los xij, lub xub ntiag ntawm IFNLR1 tivthaiv, uas yog tshwj xeeb rau hom III IFN signaling [55], tseem tsis tau piav qhia, tshwj tsis yog tias IFN-λ raug txheeb xyuas hauv kev tshawb fawb yav tom ntej. Qhov tseem ceeb, IFN thiab cytokine receptor Cheebtsam, xws li IL10R2 [54], zoo li yog ib feem ntawm ntau yam heterodimer receptor complexes uas khi sib txawv ligands [56]. Yog li, txawm tias tsis muaj IFN-λ nyob rau hauv Jamaican txiv hmab txiv ntoo puav qhia txog ib qho tshiab ligand rau cov receptor tivthaiv IFNLR1 yog ib qho kev xav.
Ob peb cov ntawv tshaj tawm dhau los tau tshaj tawm "ib txwm-ntawm IFN kev xav" uas yog ib feem ntawm kev piav qhia rau lub peev xwm tshwj xeeb ntawm cov puav kom tiv nrog cov kab mob feem ntau tuag thiab tib neeg cov kab mob [48,57,58]. Rau cov hma liab ya dub, nws tau pom tias txawm hais tias qhov kev nthuav qhia ntawm nws peb IFN- s, tsuas yog IFN- (thiab tsis ntxiv IFN-) qib nce tom qab kis tau [48].
Vim hais tias ntawm cov lus qhia ntawm IFNs, cov downstream-activated interferon-stimulated genes (ISG) tau pom tias zoo ib yam li kev koom tes hauv kev kho mob tsis txawj tuag dub ya hma liab kab lis kev cai [48]. Jamaican txiv hmab txiv ntoo puav zoo li muaj ib qho kev qhia ntawm IFN- thiab IFN- ib yam nkaus; Txawm li cas los xij, thaum kis tus kab mob TCRV, tsuas yog IFN- thiab tsis yog hom I IFN cov ntawv sau tseg tau nce siab [21]. Tsis tas li ntawd, kev kis kab mob tau ua rau muaj kev tswj hwm ntawm IFN qhia txog txoj hauv kev muaj feem cuam tshuam cov noob thiab mus rau qhov induction ntawm Isg15 thiab Irf7 [21]. Interestingly, nyob rau hauv tib txoj kev tshawb no, cov noob coding rau MHC-II tivthaiv HLADRA tau tswj tsis zoo nyob rau hauv lub raum [21]. Yog li, qhov cuam tshuam rau kev kis kab mob H18N11 uas siv MHC-II rau kev nkag mus ntawm tes tseem tsis tau raug soj ntsuam. Nyob rau hauv sib piv, Egyptian txiv hmab txiv ntoo puav tsis muaj ib qho kev qhia IFN thiab immortalized hlwb ntawm cov tsiaj no teb rau tus kab mob kis nrog induction ntawm IFN-ω thiab, txawm ntau pronounced, IFN- [49].
Ib txoj kev tshawb fawb yav dhau los tau qhia tias IFN cov lus teb yog dampened nyob rau hauv cov hma liab ya nyob rau hauv kev sib piv rau tib neeg, vim yog hloov ntawm ib tug heev conserved serine residue (S358) nrog ib tug histidine (S358H) nyob rau hauv lub stimulator ntawm IFN noob (STING) protein [59 ], uas yog xav tias thaum kawg txwv IFN- ntau lawm [60]. Ib yam li ntawd, Jamaican txiv hmab txiv ntoo puav thiab Egyptian txiv hmab txiv ntoo puav nthuav qhia qhov hloov S358H, whereas tus hma ya loj harbors ib tyrosine (S358Y) thiab me ntsis xim av puav asparagine (S358N) ntawm txoj hauj lwm no [60]. Txawm li cas los xij, txawm hais tias IFN cov cim qhia tau zoo sib xws hauv cov tsiaj no yuav tsum tau hais txog. Cov kev tshawb fawb hauv vitro tsis ntev los no kuj tau qhia tias cov hma liab ya dub thiab David's myotis bat (Myotis davidii) muaj qhov cuam tshuam NLRP3-inflammasome activation, nrog los ntawm kev txo qis hauv caspase-1 lossis IL{{11} } ua kom, thaum NF-κB signaling thiab nws cov noob tswj (Il1 , Il6, thiab Tnf ) tshwm sim tsis cuam tshuam [61,62]. Raws li, qhov nce hauv cytokine transcripts (Il6, Il8, Il1a, Il1b, thiab Ifng) tau pom hauv Jamaican txiv hmab txiv ntoo puav thaum kis kab mob [21].
Ib sab ntawm lub cev tiv thaiv kab mob hauv lub cev, cov yam ntxwv zoo ntawm Jamaican txiv hmab txiv ntoo bat adaptivetiv thaiv kab mobyuav raug txheeb xyuas. Raws li nyob rau hauv tag nrho cov vertebrates, kab mob kis tau pom ua rau humoraltiv thaiv kab mob, txawm tias titers txawv nyob ntawm tus kab mob, raws li tau piav saum toj no. Raws li tau piav qhia rau lwm hom puav [63–67], plaub immunoglobulin isotypes (IgM, IgE, IgA, thiab IgG) tau qhia hauv Jamaican txiv hmab txiv ntoo puav (Table 1) [21]. Interestingly, IgD zoo nkaus li tshwj xeeb rau insectivorous bat hom thiab yog li tsis encoded nyob rau hauv Jamaican txiv hmab txiv ntoo puav, nrog rau lwm yam frugivorous genomes, xws li lub Ntiaj Teb Tshiab Seba tus luv-tailed bat [58,65], South Asian luv luv. -nosed txiv hmab txiv ntoo bat (Cynopterus sphinx) [65], tus hma dub ya, thiab tus hma liab ya loj [45,63]. Tsuas yog ib qho subclass ntawm IgG tau txheeb xyuas nyob rau hauv ob qho tib si Jamaican txiv hmab txiv ntoo puav thiab Seba's luv-tailed bats [21], uas yog sib piv rau plaub yam IgG subclasses paub rau tib neeg, thiab ntau subclasses ntawm IgG pom nyob rau hauv nas, raws li zoo raws li me ntsis. Cov puav xim av, cov puav loj xim av (Eptiscus fuscus), thiab cov txiv hmab txiv ntoo luv-nosed ntau dua [65] (Table 1). Intriguingly, raws li TCRV kab mob ntawm Jamaican txiv hmab txiv ntoo puav, nws tau pom tias txawm tias tag nrho cov chav kawm ntawm cov tshuaj tiv thaiv tau upregulated, transcription ntawm activation-induced cytidine deaminase (AID), ib tug protein koom nyob rau hauv chav kawm-hloov recombination thiab somatic hypermutation, tsis yog.
Txawm li cas los xij, Jamaican txiv hmab txiv ntoo bat transcriptome cov ntaub ntawv qhia muaj ntau haiv neeg nyob rau hauv hnyav-chain variable (VH) cheeb tsam ntawm cov tshuaj tiv thaiv [21,58]. Qhov no yog nyob rau hauv txoj kab nrog yav dhau los cov kev tshawb fawb nyob rau hauv me ntsis xim av puav thiab ya ya hma dub, qhia hais tias combinatorial ntau haiv neeg thaum ntxov nyob rau hauv antibody ntau lawm yuav muaj feem xyuam rau lub luag hauj lwm tseem ceeb ntawm somatic hypermutation thiab affinity maturation [58,63,68]. Interestingly, me me cov puav xim av tau zoo ib yam pom tias muaj ntau hom VH repertoire thiab tsis muaj somatic hypermutation [68]. Tus hma liab ya dub, txawm tias muaj kev sib txawv ntawm VH repertoire, tau pom tias siv somatic hypermutation, txawm tias qis dua li paub rau tib neeg [63,69]. Ntxiv rau qhov kev hloov pauv hauv cov tshuaj tiv thaiv kab mob, cov hnub qub ntawm cov kab mob hloov pauv hloov pauv tau koom nrog hauv cov tshuaj tiv thaiv kab mob tshwm sim txawv ntawm tib neeg thiab thoob plaws hom puav.
Txawm hais tias cov cim ua kom muaj zog rau T thiab B lymphocytes tau raug tswj xyuas thaum kis kab mob ntawm Jamaican txiv hmab txiv ntoo puav, tib yam tsis muaj tseeb rau cov neeg tua neeg (NK) hlwb, qhia tias lawv yuav tsis tseem ceeb li tib neeg [21]. Nyob rau hauv txoj kab nrog qhov no, qhov sib luag ntawm Egyptian txiv hmab txiv ntoo bat genome qhia tias ntau ntawm cov receptor complexes koom nrog NK cell tswj thiab inhibition, nrog rau cov killer cell immunoglobulin-zoo li receptors (KIRs) [70,71], tsis tam sim no [49 ]. Tsis tas li ntawd, cov uas tau txais kev cawmdim, suav nrog ntau yam killer lectin-zoo li receptors (KLRs) uas kuj tau txheeb xyuas hauv cov hma liab ya dub [45], zoo li muaj cov motifs inhibitory, uas tej zaum yuav qhia tau tias txo lub luag haujlwm rau NK hlwb hauv cov hom no. ib [46,49].
Cov kev tshawb fawb yav dhau los hauv cov hma dub ya siv cov tshuaj tiv thaiv ntawm tes tshwj xeeb tau pom tias cov pleev ntawm cov lymphocyte cell tuaj yeem sib txawv ntawm hom [72,73]. Hauv tib neeg, B hlwb thiab T hlwb yog 3-15 feem pua thiab 40-60 feem pua , feem, ntawm peripheral ntshav mononuclear hlwb (PBMCs). Hauv cov hma ya dub, qhov feem pua siab dua rau ob hom cell (B hlwb: 29-33 feem pua, T hlwb; 62-64 feem pua) [72]. Cov kev tshawb fawb tom qab hauv lub qhov tsua nectar bat (Eonycteris spelaea) pom tias piv B thiab T cell feem pua ntawm cov poov xab, pob txha pob txha, thiab ntshav. Txawm li cas los xij, lub qhov tsua nectar puav leej tsis muaj NK hlwb nyob rau hauv ob qho tib si spleen thiab pob txha pob txha, txawm tias cov neeg ntawm tes no tseem ceeb hauv cov pob txha thiab cov pob txha ntawm cov hma dub ya [73]. Kev sim ntxiv yog yuav tsum tau txiav txim siab seb cov hlwb twg koom nrog cov tshuaj tiv thaiv kab mob tiv thaiv kab mob tiv thaiv kab mob ntawm Jamaican txiv hmab txiv ntoo puav, uas tam sim no tau txwv los ntawm qhov tsis muaj cov tshuaj tiv thaiv kab mob ntawm tes [17,21]. Tshwj xeeb tshaj yog rau txoj kev tshawb fawb ntawm H18N11, uas rov ua dua hauv cov ntaub so ntswg tiv thaiv kab mob, cov cim rau cov xov tooj sib txawv no yuav pab tau tshwj xeeb.
Yog li ntawd, kom nkag siab tag nrho lawv cov lus teb rau kev kis tus kab mob, kev sim yav tom ntej yuav tsum tau hais txog cov ntaub ntawv uas ploj lawm txog Jamaican txiv hmab txiv ntoo bat.tiv thaiv kab mob. Ua ntej, nws yuav tsum tau txiav txim siab seb lub cev tiv thaiv kab mob hauv lub cev hauv cov puav no puas yog dampened thaum kis kab mob. Qhov no suav nrog tus cwj pwm ntawm cov theem pib ntawm IFN, nrog rau cov khoom ntawm STING thiab txoj kev ua kom muaj kab mob, ob qho tib si ua ntej thiab thaum kis kab mob.
Tsis tas li ntawd, qhov sib txawv ntawm lub cev thiab lub cev tshwj xeeb ntawm cov tshuaj tiv thaiv kab mob yuav tsum raug coj mus rau hauv tus account. Cov kev tshawb fawb transcriptome yav tom ntej yuav tsum yog li ntawd tsis yog tsuas yog qhia txog cov noob caj noob ces hauv cov kab mob hauv nruab nrog cev tab sis hauv cov kab mob ntawm tus kheej thiab. Conversely, lub immunomodulatory functions ntawm viral proteins, xws li cov puav IAV IFN antagonist NS1 [74–77], yuav tsum tau txiav txim siab thaum txhais cov Jamaican txiv hmab txiv ntoo puav lub cev tiv thaiv kab mob.
Ua ke, cov kev soj ntsuam ua rau cov kab sib txawv qhia tau hais tias muaj ntau yam kev qhia txog tus puavtiv thaiv kab mobNws tsis zoo li tuav thiab qhia txog kev tiv thaiv kab mob ntau dua rau kev kis kab mob. Qhov no tsis yog qhov xav tsis thoob, xav tias muaj ntau dua 1400 hom puav nyob rau hauv qhov kev txiav txim Chiroptera uas tshwm sim tsawg kawg yog 64 lab xyoo dhau los [78]. Muab qhov zoo tshaj plaws kev tiv thaiv kab mob sib txawv no, nws tau dhau los ua qhov tseeb tias cov kab sib txawv thiab lawv cov lus teb tiv thaiv kab mob sib koom ua ke nrog cov kab mob uas lawv nyob hauv. Yuav kom kawm paub cov kab mob tiv thaiv kab mob kom raug, yuav tsum siv qhov tseeb tus kab mob-tus tswv tsev. Txog Jamaican txiv hmab txiv ntoo puav, kev tshawb fawb ntxiv siv tus qauv tsim nyog cov kab mob yuav sau rau hauv qhov seem seem ntawm qhov kev paub tam sim no ntawm nws.tiv thaiv kab mobthiab tshawb nrhiav cov kab mob sib kis, tshwj xeeb tshaj yog kev ua haujlwm ntawm immunomodulatory, uas yuav tso cai rau cov kab mob nkag mus rau hauv cov hlwb, rov ua dua, thiab kis tau ntawm cov kab no yam tsis muaj kev puas tsuaj loj.
Tus sau kev koom tes:
QD thiab KC tsim lub tswv yim txheej txheem thiab sau cov qauv qub. MS thiab TS kho thiab kho cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Nyiaj txiag:
Qhov project no tau txais nyiaj los ntawm European Research Council (ERC) nyob rau hauv European Union's Horizon 2020 kev tshawb fawb thiab kev tsim kho tshiab (daim ntawv pom zoo No 882631)" rau MS thiab US National Institute of Allergy thiab Kab Mob Sib Kis (AI134768, AI140442) thiab National Science. Foundation (2033260) to TS
Institutional Review Board Statement:
Tsis siv tau.
Cov Lus Qhia Txog Kev Pom Zoo:
Tsis siv tau.
Kev tsis sib haum xeeb ntawm kev txaus siab:
Cov kws sau ntawv tshaj tawm tsis muaj kev sib cav txog kev txaus siab. Cov nyiaj txiag tsis muaj lub luag haujlwm hauv kev tsim thiab sau cov ntawv sau, lossis hauv kev txiav txim siab tshaj tawm cov txiaj ntsig.
Cov ntaub ntawv
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