As­saf Var­di: The me­ta­bo­lic cross talk du­ring host-vi­rus arms race at sea

Ma­ri­ne vi­ru­s­es are re­co­gni­zed as ma­jor eco­lo­gi­cal and evo­lu­tio­na­ry dri­ving forces, shaping com­mu­ni­ty struc­tu­re and con­trol­ling cy­cling of nut­ri­ent en­er­gy in the ma­ri­ne en­vi­ron­ment. A ma­jor chal­len­ge in our cur­rent un­der­stan­ding of host-vi­rus in­ter­ac­tions dy­na­mics is to de­co­de the wealth of ge­no­mic data and trans­la­te it into cel­lu­lar me­cha­nisms that me­dia­te host sus­cep­ti­bi­li­ty and re­sis­tan­ce to vi­ral in­fec­tion. Fur­ther­mo­re, our abili­ty to as­sess the eco­lo­gi­cal im­pact of ma­ri­ne vi­ru­s­es is cur­rent­ly li­mi­ted to ap­proa­ches that fo­cus main­ly on quan­ti­fi­ca­ti­on of vi­ral di­ver­si­ty.

We in­ves­ti­ga­te the in­ter­ac­tions bet­ween the cos­mo­po­li­tan bloom-for­ming alga Emiliania huxleyi and its spe­ci­fic lar­ge dsD­NA vi­rus EhV that is re­s­pon­si­ble for lar­ge sca­le bloom de­mi­se. The­re­fo­re, this host-pa­tho­gen mo­del is an attrac­tive sys­tems to elu­ci­da­te ba­sic me­ta­bo­lic prin­ci­ples that me­dia­te the fate and out­co­me of this in­ter­ac­tion. Re­cent­ly, we re­vea­led how in­fec­tion by EhV in­du­ced pro­found re­wiring host me­ta­bo­lic pa­thways (e.g. sphin­go­li­pids, TAGs, re­dox and au­to­pha­gy), which are cri­ti­cal for vi­ral as­sem­bly and egress.

Host-pa­tho­gen in­ter­ac­tions are high­ly dy­na­mic, in­vol­ving a com­plex host de­fen­se and pa­tho­gen hi­jacking stra­te­gies. In­ves­ti­ga­ting the­se in­ter­ac­tions at the who­le-po­pu­la­ti­on le­vel tends to mask cell-to-cell va­ria­bi­li­ty, ham­pe­ring the abili­ty to dis­cern bet­ween di­ver­se phe­no­ty­pes. Here we un­mas­ked al­gal host re­s­pon­ses to vi­ral in­fec­tion, by re­sol­ving host-vi­rus in­ter­ac­tions on a sin­gle cell re­so­lu­ti­on, by com­bi­ning sin­gle-cell dual RNA-seq with ad­van­ced mass spec­tro­me­try ima­ging. We used clus­te­ring of in­di­vi­du­al cells ba­sed on their spe­ci­fic tran­scrip­to­mic si­gna­tu­res and uni­que me­ta­bo­lic pro­filing, to de­fi­ne dis­tinct “in­fec­tion sta­tes” and to un­mask rare re­sis­tant phe­no­ty­pes. Re­sol­ving host-vi­rus “arms race” on a sin­gle cell le­vel will pro­vi­de no­vel sen­si­ti­ve bio­mar­kers to quan­ti­fy ac­tive vi­ral in­fec­tion and to as­sess the eco­lo­gi­cal im­pact of ma­ri­ne vi­ru­s­es and their func­tion in re­gu­la­ting the fate of al­gal blooms in the oce­an.