A Most Lively Virus – and an Ad­den­dum

We re-post this won­der­ful piece by Merry from nearly twelve years ago and add a brief ac­count of an ex­cit­ing new de­vel­op­ment on the topic of ar­chaeal viruses. We know Merry, who had an in­or­di­nate fond­ness for bac­ter­iophages, would have loved to write about it!

by Merry (†) and the STC team

Mor­pho­log­i­cally speak­ing, the viruses of mesophilic and mod­er­ately ther­mophilic bac­te­ria and ar­chaea are a dull bunch. Of 5,100 sur­veyed, 97% are ho-hum head-and-tail phages – icosa­he­dral heads with he­li­cal tails. The remain­der were tail­less icosa­he­dra or fil­a­ments, ex­cept for two spin­dle-shaped odd­balls. If you'd like more struc­tural ex­citement, best to go virus hunt­ing in ge­ot­her­mally-heated aquatic en­vi­ron­ments above 80 ºC – the hot springs, mud holes, and deep-sea hy­drother­mal vents – and be pre­pared to be as­ton­ished.

TEMs of a va­ri­ety of viruses and virus-like par­ti­cles ob­served in a sin­gle en­rich­ment cul­ture es­tab­lished from a sam­ple col­lected at a Yel­low­stone hot acidic spring (85°C, pH 1.5–2.0). Bar = 200 nm (100 nm for in­sets). Source

Here the sta­tis­tics are re­versed. Only 6% re­sem­ble typ­i­cal head-and-tail phages; an­other 6% are tail­less icosahe­drons; about two-thirds are fil­a­men­tous, rod-shaped, or spin­dle-shaped; the rest are truly unique. The odd­est ones are viruses of hy­per­ther­mophilic Cre­nar­chaeota of the gen­era Sul­folobus, Acid­i­anus, Py­robac­u­lum and Ther­mo­pro­teus. About two dozen of these have been iso­lated and char­ac­ter­ized, call­ing for the cre­ation of seven new vi­ral fam­i­lies to house them. All have ds­DNA genomes, some lin­ear and some cir­cu­lar. Al­most all es­chew host ly­sis, opt­ing in­stead for a sta­ble lyso­genic re­la­tion­ship. Maybe life out­side is just a lit­tle too tough.

TEM of ATV viri­ons in an en­riched sam­ple taken from acidic hot springs in Pozzu­o­li/IT (pH 1.5, 85–93ºC). Source

Here's one par­tic­u­larly fas­ci­nat­ing ex­am­ple iso­lated in 2005 from an acidic hot spring (85–93ºC; pH 1.5) at Poz­zuoli, Italy. En­rich­ment cul­tures con­tained un­usual foot­ball-shaped virus-like par­ti­cles with tails of vary­ing lengths at each end. (The re­searchers de­scribe them as "lemon-shaped," but lemons, at least in Hawaii, feel no oblig­a­tion to re­sem­ble the Sunkist stereo­type in ei­ther shape or color. "Foot­ball-shaped" isn't per­fect ei­ther; foot­balls in some parts of the world are round.) These strange par­ti­cles be­have like re­spectable viruses, repli­cating in cells of the ar­chaeon Acid­i­anus con­vi­va­tor. This virus, the Acid­i­anus two-tailed virus (ATV), has a fam­ily all to it­self: the Bi­cau­daviri­dae (two-tailed viruses). Av­er­age length end-to-end for par­ti­cles with fully de­vel­oped tails is 744 nm.

Tem­per­a­ture mat­ters to these viruses. When they in­fect at 85ºC, the op­ti­mum tem­per­a­ture for their host, they lyso­g­e­nize. When the lyso­gens are experi­mentally sub­jected to a 75ºC "cold shock," the virus goes lytic, lysing the cells and re­leas­ing abun­dant viri­ons four days later.

b TEM show­ing ex­tru­sion of foot­ball-shaped ATV viri­ons from an A. con­vi­va­tor cell. c newly re­leased viri­ons. Bar = 0.5 µm. Source

If you are won­der­ing how a bunch of three-quar­ters-of-a-mi­cron-long viri­ons are ac­com­mo­dated within the host cell prior to ly­sis, the an­swer is that they are not. The vi­rions emerge as foot­balls; the tails form af­ter­wards. This strik­ing trans­for­ma­tion does not re­quire cell con­tact, an ex­oge­nous en­ergy source, or co-fac­tors, and as such is unique within the known vi­ral world. A few other viruses un­dergo lim­ited struc­tural changes upon ad­sorp­tion to a host cell or dur­ing bud­ding from one, but this marked ac­tiv­ity of ATV viri­ons is host-in­de­pen­dent, and a lively ex­cep­tion to our de­f­i­n­i­tion of viri­ons as in­ert pack­ages.

Why two tails? Why such long tails? The re­searchers note that ATV is the only virus of an acido­philic hy­per­ther­mophile known to lyse its host, al­beit only un­der stress con­di­tions. Thus, un­like those that stay in­doors, ATV is con­fronted with a hos­tile en­vi­ron­ment where host cells are sparse. The tails triple their length, greatly in­creas­ing their chances of quickly bump­ing into a po­ten­tial host cell.

ATV virion. (a) TEM. (b) Three-di­men­sional reconstruc­tion by elec­tron to­mog­ra­phy of the tail re­gion shown in the in­set. Ar­row = in­ter­nal 2 nm fil­a­ment. Bar = 100 nm in (a), 50 nm in (b). Source

How the tails are formed re­mains a mys­tery. The process is tem­per­a­ture de­pen­dent. Tail­less new­born par­ti­cles can be held at 4ºC for sev­eral months, and still sprout no tails. At 75ºC, they grow tails, but very slowly, tak­ing ~8 days. Given their pre­ferred 85ºC they com­plete the job in less than an hour. In the process, the par­ti­cles shrink to about half their orig­i­nal vol­ume (even al­low­ing for the vol­ume of the tails.)
 

Ad­den­dum

The world of ar­chaeal viruses con­tin­ues to pro­vide us with re­mark­able new bi­ol­ogy. The re­cent pa­per by Jun­feng Liu and col­leagues de­scribes how in­fec­tion of the ar­chaeon Sul­folobus is­landi­cus by the non-lytic lemon-shaped virus STSV2 leads to dra­matic changes in cell mor­phol­ogy. The virus in­ter­feres with the host's cell cy­cle, ar­rest­ing it in S phase. In­fec­tion also re­presses tran­scrip­tion of the genes en­cod­ing the cell di­vi­sion ma­chin­ery. Con­se­quently, infect­ed cells grow dra­mat­i­cally larger, reach­ing vol­umes 8,000-fold greater than un­in­fected cells. And in­stead of di­vid­ing by bi­nary fis­sion, these gi­ant cells be­gin to re­pro­duce through asym­met­ric di­vi­sion. By bud­ding, much like yeast cells! If re­in­fected, these new­born cells also be­come gi­ants. But there's a twist. If the host has a CR­SIPR-Cas sys­tem, the gi­ant cells ac­quire virus-de­rived spac­ers and ter­mi­nat­ing the spread of the virus. It is sim­ply amaz­ing how this archae­al virus ma­nip­u­lates the cell to con­vert it into a gi­ant virion-pro­duc­ing fac­tory!

Virus-In­duced Cell Gi­gan­tism. Top: un­in­fected cells. Mid­dle: 1 day post in­fec­tion. Bot­tom: 6 days post in­fection. Scale bar = 1 µm. Adapted from Source

 

Ref­er­ences

Häring M, Vester­gaard G, Rachel R, Chen L, Gar­rett RA, Prangishvili D. 2005. Vi­rol­ogy: in­de­pen­dent virus de­vel­op­ment out­side a host. Na­ture, 436 (7054), 1101–1102. PMID 16121167

Liu J, Cvirkaite-Krupovic V, Ba­quero DP, Yang Y, Zhang Q, Yu­long Shen Y, Krupovic M. 2021. Virus-in­duced cell gi­gan­tism and asym­met­ric cell di­vi­sion in ar­chaea. Proc Natl Acad Sci USA, 118 (15), e2022578118. PMID 33782110

Prangishvili D, Vester­gaard G, Häring M, Ara­mayo R, Basta T, Rachel R, & Gar­rett RA. 2006. Struc­tu­ral and ge­nomic prop­er­ties of the hy­per­ther­mophilic ar­chaeal virus ATV with an ex­tra­cel­lu­lar stage of the re­pro­duc­tive cy­cle. J Mol Biol, 359 (5), 1203–1216. PMID 16677670