diff --git a/content/3.defense-systems/drt.md b/content/3.defense-systems/drt.md
index 3fce08172b854036a62d9d23cdbb40809ce8188a..4297087b3f5db4bd9507e9fdb777c0920136c903 100644
--- a/content/3.defense-systems/drt.md
+++ b/content/3.defense-systems/drt.md
@@ -10,9 +10,37 @@ tableColumns:
Activator: Unknown
Effector: Unknown
PFAM: PF00078
+contributors:
+ - Helena Shomar
+ - Marie Guillaume
+relevantAbstracts:
+ - doi: 10.1093/nar/gkac467
+ - doi: 10.1126/science.aba0372
---
# DRT
+
+## Description
+DRT stands for Defense-associated Reverse Transcriptases.
+DRTs are a widespread and highly diverse family of defense systems, characterized by reverse transcriptase (RTs) components with antiphage properties. These RTs belong to the so-called group of unknown RTs (UG) and are closely related to the Abortive Infection system (Abi) RTs.
+
+DRT systems were experimentally validated in _Escherichia coli_ and demonstrated to be effective against an array of diverse phages.
+So far, DRTs have been classified in 9 different types. Essential components of each DRT type are:
+- DRT Type 1: UG1 (RT-nitrilaseTM domains)
+- DRT Type 2: UG2 (RT domain)
+- DRT Type 3: UG3 (RT domain), UG8 (RT domain) and ncRNA
+- DRT Type 4: UG15 (RT-alphaRep domains)
+- DRT Type 5: UG16 (RT domain)
+- DRT Type 6: UG12 (RT-alphaRep domains)
+- DRT Type 7: UG10 (PrimS-RT-alphaRep domains)
+- DRT Type 8: UG7 (RT-alphaRep-PDDExK domains)
+- DRT Type 9: UG28 (RT-alphaRep domains) and ncRNA
+
+
+## Molecular mechanism
+To our knowledge, the molecular mechanism is unknown.
+Similarly, for the other systems of this family, the molecular mechanism remain unknown.
+
## Example of genomic structure
A total of 9 subsystems have been described for the DRT system.
@@ -187,7 +215,7 @@ Escherichia coli
Origin_3[ RT UG15 Type 4
Escherichia coli
<a href='https://ncbi.nlm.nih.gov/protein/GCK53192.1'>GCK53192.1</a>] --> Expressed_3[Escherichia coli]
- Expressed_3[Escherichia coli] ----> T5 & T3 & T7 & Phi-V1 & ZL19
+ Expressed_3[Escherichia coli] ----> T5 & T3 & T7 & Phi-V1 & ZL-19
Gao_2020[<a href='https://doi.org/10.1126/science.aba0372'>Gao et al., 2020</a>] --> Origin_4
Origin_4[ RT UG16 Type 5
Escherichia coli
@@ -251,12 +279,12 @@ end
T3
T7
Phi-V1
- ZL19
+ ZL-19
T5
T3
T7
Phi-V1
- ZL19
+ ZL-19
T2
T2
T5
@@ -272,14 +300,5 @@ end
style Title3 fill:none,stroke:none,stroke-width:none
style Title4 fill:none,stroke:none,stroke-width:none
</mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1093/nar/gkac467
- - doi: 10.1126/science.aba0372
----
-::
diff --git a/content/3.defense-systems/gao_mza.md b/content/3.defense-systems/gao_mza.md
index eef4cf639415a047e895ef6522630eb20c25b1c6..837f52188a2ad4eaa5ac06b61bf41846db13f20f 100644
--- a/content/3.defense-systems/gao_mza.md
+++ b/content/3.defense-systems/gao_mza.md
@@ -10,9 +10,20 @@ tableColumns:
Activator: Unknown
Effector: Unknown
PFAM: PF00023, PF04542, PF04545, PF10592, PF10593, PF13589, PF13606, PF14390
+contributors:
+ - Hugo Vaysset
+relevantAbstracts:
+ - doi: 10.1126/science.aba0372
---
# Gao_Mza
+
+## Description
+Mza (MutL, Z1, DUF, AIPR) is a defense system composed of five proteins. Its antiphage activity was assessed by heterologous expression in *E. coli* against phages T2, T4, T5, lambda and M13 (ssDNA phage) :ref{doi=10.1126/science.aba0372}.
+
+## Molecular mechanism
+As far as we are aware, the molecular mechanism is unknown.
+
## Example of genomic structure
The Gao_Mza is composed of 5 proteins: MzaA, MzaB, MzaC, MzaD and MzaE.
@@ -103,13 +114,4 @@ end
style Title3 fill:none,stroke:none,stroke-width:none
style Title4 fill:none,stroke:none,stroke-width:none
</mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1126/science.aba0372
-
----
-::
diff --git a/content/3.defense-systems/lit.md b/content/3.defense-systems/lit.md
index 58c86a7a989183b25b6aebd58b63acea08e5a9ea..701cbb9005c5c290890bf1cc0696c73452564f1a 100644
--- a/content/3.defense-systems/lit.md
+++ b/content/3.defense-systems/lit.md
@@ -3,16 +3,33 @@ title: Lit
layout: article
tableColumns:
article:
- doi: 10.1186/1743-422X-7-360
+ doi: 10.1073/pnas.91.2.802
abstract: |
- Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC) and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit); and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes) of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.
+ Bacteriophage T4 multiples poorly in Escherichia coli strains carrying the defective prophage, e14; the e14 prophage contains the lit gene for late inhibitor of T4 in E. coli. The exclusion is caused by the interaction of the e14-encoded protein, Lit, with a short RNA or polypeptide sequence encoded by gol from within the major head protein gene of T4. The interaction between Lit and the gol product causes a severe inhibition of all translation and prevents the transcription of genes downstream of the gol site in the same transcription unit. However, it does not inhibit most transcription, nor does it inhibit replication or affect intracellular levels of ATP. Here we show that the interaction of gol with Lit causes the cleavage of translation elongation factor Tu (EF-Tu) in a region highly conserved from bacteria to humans. The depletion of EF-Tu is at least partly responsible for the inhibition of translation and the phage exclusion. The only other phage-exclusion system to be understood in any detail also attacks a highly conserved cellular component, suggesting that phage-exclusion systems may yield important reagents for studying cellular processes.
Sensor: Monitoring host integrity
Activator: Direct
Effector: Other (Cleaves an elongation factor, inhibiting cellular translation
PFAM: PF10463
+contributors:
+ - Lucas Paoli
+relevantAbstracts:
+ - doi: 10.1128/jb.169.3.1232-1238.1987
+ - doi: 10.1128/jb.170.5.2056-2062.1988
+ - doi: 10.1073/pnas.91.2.802
+ - doi: 10.1074/jbc.M002546200
+ - doi: 10.1186/1743-422X-7-360
---
# Lit
+
+## Description
+
+Lit was first identified in 1989 :ref{doi=10.1128/jb.169.3.1232-1238.1987}, stands for late inhibitors of T4, and was found to inhibit phage T4 in Escherichia coli (K12). The Lit gene is found in the e14 cryptic prophage :ref{doi=10.1128/jb.170.5.2056-2062.1988}. Lit is also partially active against other T-even phages :ref{doi=10.1073/pnas.91.2.802}.
+
+## Molecular mechanisms
+
+The Lit system detects cleaves EF-Tu translation factor :ref{doi=10.1073/pnas.91.2.802} at a late stage of phage maturation, when the major capsid protein binds to EF-Tu and triggers its cleavage by Lit :ref{doi=10.1074/jbc.M002546200}. As a result, the translation is inhbited, which ultimately leads to cell death. Lit is part of the abortive infection category of defense systems.
+
## Example of genomic structure
The Lit is composed of 1 protein: Lit.
@@ -69,15 +86,3 @@ end
style Title3 fill:none,stroke:none,stroke-width:none
style Title4 fill:none,stroke:none,stroke-width:none
</mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1073/pnas.91.2.802
- - doi: 10.1074/jbc.M002546200
- - doi: 10.1186/1743-422X-7-360
-
----
-::
-
diff --git a/content/3.defense-systems/mok_hok_sok.md b/content/3.defense-systems/mok_hok_sok.md
index 17683a2176fa013dc98ca58a9d422805e82726b1..a7bc48e602010cf139920842f9cbcdd000bd9cd1 100644
--- a/content/3.defense-systems/mok_hok_sok.md
+++ b/content/3.defense-systems/mok_hok_sok.md
@@ -10,9 +10,26 @@ tableColumns:
Activator: Unknown
Effector: Unknown
PFAM: PF01848
+relevantAbstracts:
+ - doi: 10.1128/jb.178.7.2044-2050.1996
+ - doi: 10.1016/0022-2836(92)90714-u
+contributors:
+ - Jean Cury
---
# Mok_Hok_Sok
+
+## Description
+
+The Mok Hok Sok system was discovered as a type 1 toxin-antitoxin system to stabilize plasmid R1 :ref{doi=10.1128/jb.161.1.292-298.1985}. Sok (Suppression of Killing) is an RNA and serves as the antitoxin. Hok (Host killing) is the toxin and Mok (Modulation of killing) is required for the expression of Hok :ref{doi=10.1016/j.mib.2007.03.003,10.1093/nar/gkl750}.
+Hok/sok are not related to the T4 head protein Hoc and Soc.
+This system defends against T4 phages only, as far as we currently know.
+
+## Molecular mechanism
+
+Upon infection of phage T4, the transcription is halted by the phage, which leads to a decreasing level of the antitoxin Sok within a few minutes. The Hok proteins manage to be process in their active form and trigger cell death by depolarization of the membrane :ref{doi=10.1006/jmbi.1995.0186} before the later stage of the phage infection (assembly, packaging and lysis).
+
+
## Example of genomic structure
The Mok_Hok_Sok is composed of 2 proteins: Mok and Hok.
@@ -51,7 +68,7 @@ graph LR;
Pecota_1996[<a href='https://doi.org/10.1128/jb.178.7.2044-2050.1996'>Pecota and Wood, 1996</a>] --> Origin_0
Origin_0[R1 plasmid of Salmonella paratyphi
<a href='https://ncbi.nlm.nih.gov/protein/WP_001372321.1'>WP_001372321.1</a>] --> Expressed_0[Escherichia coli]
- Expressed_0[Escherichia coli] ----> T4 & LambdaVir
+ Expressed_0[Escherichia coli] ----> T4
subgraph Title1[Reference]
Pecota_1996
end
@@ -63,20 +80,10 @@ end
end
subgraph Title4[Phage infected]
T4
- LambdaVir
end
style Title1 fill:none,stroke:none,stroke-width:none
style Title2 fill:none,stroke:none,stroke-width:none
style Title3 fill:none,stroke:none,stroke-width:none
style Title4 fill:none,stroke:none,stroke-width:none
</mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1128/jb.178.7.2044-2050.1996
-
----
-::
diff --git a/content/3.defense-systems/viperin.md b/content/3.defense-systems/viperin.md
index a5965d930cb54da720544cf0bd889aa356aecc79..7fcc72e1252ec82e81e7541609d26389e3426e0a 100644
--- a/content/3.defense-systems/viperin.md
+++ b/content/3.defense-systems/viperin.md
@@ -7,28 +7,32 @@ tableColumns:
abstract: |
Viperin is an interferon-induced cellular protein that is conserved in animals. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3'-deoxy-3',4'-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems.
Sensor: Unknown
- Activator: Direct
+ Activator: Direct binding
Effector: Nucleotide modifying
PFAM: PF04055, PF13353
+contributors:
+ - Marian Dominguez-Mirazo
+relevantAbstracts:
+ - doi: 10.1038/s41586-020-2762-2
---
# Viperin
## Description
-Viperins, for "Virus Inhibitory Protein, Endoplasmic Reticulum-associated, INterferon-inducible", are antiviral enzymes whose expression is stimulated by interferons in eukaryotic cells. They are important components of eukaryotic innate immunity, and present antiviral activity against a wide diversity of viruses, including double-stranded DNA viruses, single-strand RNA viruses and retroviruses (1). Â
+Viperins, for "Virus Inhibitory Protein, Endoplasmic Reticulum-associated, INterferon-inducible", are antiviral enzymes whose expression is stimulated by interferons in eukaryotic cells. They are important components of eukaryotic innate immunity, and present antiviral activity against a wide diversity of viruses, including double-stranded DNA viruses, single-strand RNA viruses and retroviruses :ref{doi=10.1146/annurev-virology-011720-095930}. Â
-Recently, Â Viperin-like enzymes were found in prokaryotes (pVips). Â Strikingly, like their eukaryotic counter-part with eukaryotic viruses, pVips provide clear protection against phage infection to their host, and therefore constitute a new defense system (2). Like eukaryotic Viperins, pVips produce modified nucleotides that block phage transcription, acting as chain terminators. They constitute a form of chemical defense. A recent study reported that pVips can be found in around 0.5% of prokaryotic genomes (3).
+Recently, Â Viperin-like enzymes were found in prokaryotes (pVips). Â Strikingly, like their eukaryotic counter-part with eukaryotic viruses, pVips provide clear protection against phage infection to their host, and therefore constitute a new defense system :ref{doi=10.1038/s41586-020-2762-2}. Like eukaryotic Viperins, pVips produce modified nucleotides that block phage transcription, acting as chain terminators. They constitute a form of chemical defense. A recent study reported that pVips can be found in around 0.5% of prokaryotic genomes :ref{doi=10.1038/s41467-022-30269-9}.
## Molecular mechanism
+!Figure1](/viperin/human_vip.jpg){max-width=750px}
+Fig.1: Catalytic activity of human Viperin generates ddhCTP :ref{doi=10.1002/1873-3468.13778}
-Fig.1: Catalytic activity of human Viperin generates ddhCTP (Ebrahimi et al. al., 2020)
-
-Viperins are members of the radical S-adenosylmethionine (rSAM) superfamily. This group of enzymes use a [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) reductively, generating a radical which is generally transferred to a substrate. It was demonstrated that through their [4Fe-4S] cluster catalytic activity, eukaryotic viperins convert a ribonucleotide, the cytidine triphosphate (CTP) into a modified ribonucleotide, the 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) (4,5).Â
+Viperins are members of the radical S-adenosylmethionine (rSAM) superfamily. This group of enzymes use a [4Fe-4S] cluster to cleave S-adenosylmethionine (SAM) reductively, generating a radical which is generally transferred to a substrate. It was demonstrated that through their [4Fe-4S] cluster catalytic activity, eukaryotic viperins convert a ribonucleotide, the cytidine triphosphate (CTP) into a modified ribonucleotide, the 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) :ref{doi=10.1038/s41586-018-0238-4}.Â
-Prokaryotic Viperins also convert ribonucleotides triphosphate into modified ribonucleotides, but contrary to their eukaryotic counterparts can use a diversity of substrates to produce  ddhCTP,  or ddh-guanosine triphosphate (ddhGTP), or ddh-uridine triphosphate (ddhUTP), or several of these nucleotides for certain pVips (2).
+Prokaryotic Viperins also convert ribonucleotides triphosphate into modified ribonucleotides, but contrary to their eukaryotic counterparts can use a diversity of substrates to produce  ddhCTP, or ddh-guanosine triphosphate (ddhGTP), or ddh-uridine triphosphate (ddhUTP), or several of these nucleotides for certain pVips :ref{doi=10.1038/s41586-020-2762-2}.
-Compared to the initial ribonucleotide triphosphate, the modified ddh-nucleotide product of Viperins lacks a hydroxyl group at the 3′ carbon of the ribose (Fig.1). The ddh-nucleotides produced by Viperins can be used as substrates by some viral RNA polymerases. Because of their lost hydroxyl group at the 3’carbon of the ribose, once incorporated into the newly forming viral RNA chain, these ddh-nucleotides act as chain terminators. By preventing further polymerization of the viral RNA chain, ddh-nucleotides can inhibit viral replication (2,4,5).
+Compared to the initial ribonucleotide triphosphate, the modified ddh-nucleotide product of Viperins lacks a hydroxyl group at the 3′ carbon of the ribose (Fig.1). The ddh-nucleotides produced by Viperins can be used as substrates by some viral RNA polymerases. Because of their lost hydroxyl group at the 3’carbon of the ribose, once incorporated into the newly forming viral RNA chain, these ddh-nucleotides act as chain terminators. By preventing further polymerization of the viral RNA chain, ddh-nucleotides can inhibit viral replication :ref{doi=10.1038/s41586-020-2762-2,10.1038/s41586-018-0238-4}.
## Example of genomic structure
@@ -223,13 +227,4 @@ end
style Title3 fill:none,stroke:none,stroke-width:none
style Title4 fill:none,stroke:none,stroke-width:none
</mermaid>
-## Relevant abstracts
-
-::relevant-abstracts
----
-items:
- - doi: 10.1038/s41586-020-2762-2
-
----
-::
diff --git a/public/viperin/human_vip.jpg b/public/viperin/human_vip.jpg
new file mode 100644
index 0000000000000000000000000000000000000000..a2d9fead78af888a5cc74088bec06bad8b3b8dea
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