m124a article review

7/23/2019 M124a Article Review

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ABSTRACT

- Lloviu virus (LLOV) is a new member of the lovirus family whichincludes Ebola virus (EBOV) and Marburg virus (M!V)

- EBOV V"#$ and M!V V"#$ inhibit interferon (%&')-alhabetaroduction

- EBOV V"#$ bloc*s activation of antiviral *inase "+!- EBOV V", and M!V V". inhibit %&' signaling- LLOV V"#$ suresses /endai virus induced %&' regulatory factor #

(%!) hoshorylation0 %&'-alhabeta roduction0 and "+!hoshorylation

- LLOV V", bloc*s tyrosine hoshorylated /112 binding to*aryoherin alha $ (+"'$)0 /112 nuclear accumulation0 and %&'-induced gene e3ression

- LLOV V". lac*s detectable %&' antagonist function- EBOV 4 LLOV V"#$ and V", inhibit %&' resonses in bat cells- 1herefore0 LLOV infection will bloc* innate immune resonses similar to

EBOV

INTRODUCTION

- LLOV was found in bat carcasses- "5! se6uencing showed comlete genome- LLOV was assigned to family &iloviridae (which includes EBOV and

M!V)- EBOV and M!V have singled stranded negative-sense !' genome

with 7 oen reading frames (O!&)- 7 O!&8 '"0 V"#$0 V".0 9"0 V"#.0 V", and L roteins- EBOV V"#$ and M!V V"#$ bloc* !%9-%-li*e recetor (!L!) signaling

athways and imair %&'-alhabeta roduction- !L! is suosed to sense !'s with $:-trihoshates or ds!'s and

romote the hoshorylation and activation of interferon regulatoryfactor # (%!)

- EBOV V"#$ inhibits activation of %&'-induced antiviral *inase "+!- EBOV V", and M!V V". bloc*s the %&' induced ;+-/11 signaling

athway- EBOV V", revents nuclear translocation of tyrosine hoshorylated

/112- M!V V". inhibits %&' signaling at level of ;+2 hoshorylation- LLOV:s ability to infect cells is unclear0 but LLOV 9" rotein was shown

to enter human cells using similar mechanisms as other loviral 9"s- LLOV. had no detectable antagonistic function- LLOV is caable of evading human and bat innate immune resonses

by mechanisms similar to EBOV

RESULTS

- LLOV O!&s encoded V",0 V"#$0 and V".- !eorter gene assays were erformed


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- EBOV V"#$ rotein targets stes in !%9-% signaling athway0 leading toinhibition of %&'-beta gene e3ression and %! hoshorylation

- Both human and bat cells were transfected with lasmids for %! incombination with EBOV V"#$ and LLOV V"#$> Emty vectors used ascontrols

- EBOV and LLOV V"#$ comletely inhibited hoshorylation of %!

- EBOV V"#$ inhibits hoshorylation and activation of "+!

- Both human and bat cells were tranfected with EBOV V"#$0 LLOV V"#$0or emty vector> 1hen infected with /eV to induce "+! hoshorylation

- LLOV V"#$ inhibited "+! hoshorylation to a lesser e3tent than EBOVV"#$0 but functions mirror each other in inhibiting "+! hoshorylation


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- EBOV V", bloc*s tye 2 %&' signaling athway (more secicallyEBOV V", binds '"%-2 subfamily of *aryoherin alha (+"') roteins0reventing +"' interaction with /112 and its subse6uenttranslocation to nucleus

- Ased immunouorescence assay to assess the intracellular locali?ationof /112 in resence of LLOV V",

- Vero7C and bat cells were transfected with emty vector0 EBOV V",0and LLOV V",

- %&' treated human and bat cells over-e3ressing LLOV V", and EBOVV", inhibited /112 nuclear translocation and remained cytolasmic

- 1he emty vectors treated with %&' showed /112 that wasredominantly nuclear

- 5o-immunoreciitation assay erformed to determine whether altered/112 locali?ation in resence of LLOV V", correlated with its abilityto bloc* /112 binding to +"'$

-


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- EBOV V". and LLOV V". are CD identical in amino acids0 so li*eEBOV V".0 LLOV V". also fails to inhibit %&'-beta and %/9$romoter activity in humans and bat cells

m124a article review

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