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== Introduction: ==
Vertebrate retroviruses (''Retroviridae'') are restricted to vertebrate animals. They are viral particles that reverse transcribe their RNA genome into a double stranded DNA copy that is inserted into the infected host cell genome. Their diploid RNA genome is enveloped within a protein capsid by a membrane fragment of the host cell in which env antigens are embedded.

== Genomic structure: ==
''Retroviridae'' originally received attention when infectious representatives were characterized in humans. However, it is now known that any LTR retrotransposon capable of recruiting a third ORF envelope gene (''env'') is potentially capable of becoming a retrovirus (''env'' is the most basic difference between LTR retrotransposons and retroviruses). In fact, the ''Retroviridae'' display a gag-pol structure similar to that presented by ''Ty3/Gypsy'' LTR retroelements; the absence or presence of an ''env'' gene is the main difference between a ''Ty3/Gypsy'' LTR retrotransposon and a potential ''Ty3/Gypsy'' or ''Retroviridae'' simple retrovirus ([[Ty3_Gypsy|see ''Ty3/Gypsy'' family]]).

A canonical viral RNA genome consists of ~10Kb of RNA (+) with a 5'Cap and a 3'poly-A tail ([[Literature:81403|Wang ''et al''. 1975]]; [[Literature:14008|Coffin and Billeter 1976]]).

In 5'-3' direction the viral RNA is structured as follows:

*A 5'direct repeat (R) of 18-250 nt
*A non-coding region of 75-250 nt (U5) that corresponds to the first portion of the retrotranscribed genome.
*A Primer Binding Site (PBS) of 18 nt, complementary to a specific zone of the 3' end of a tRNA normally provided by the host cell to start the retrotranscription.
*Open Reading Frames (ORFs) for ''gag, pol, and env'' genes and other accessory genes (in the case of complex retroviruses).
*A small region of ~10 A/G "Polypurine Tract" (PPT), responsible for starting the synthesis of the proviral (+) DNA strand.
*A non-coding zone of 200-1.200 nt (U3) containing the zone of promoters and constituting the 5' end of the proviral DNA.
*A 3'direct repeat (R) of 18-250 nt.

The retroviral RNA presents the same structural phenotype than cellular mRNAs. Its function, however, differs from that performed by cellular mRNAs in that following the infecting process, a retrovirus retrotranscribes itself in order to be inserted in the host cell as a proviral genome of DNA.

[[Image:Retroviridae_all_1.gif|center]]

Prior to the integration, in the transcribing process the U3 zone is reordered upstream to the R and U5 zones generating a new LTR zone (U3/R/U5), which is subsequently duplicated (see LTRs formative process).

[[Image:Retroviridae_all_2.gif|center]]

The ''gag'' gene codifies for a gag polyprotein containing the matrix (MA), capsid (CA) and the nucleocapsid (NC) domains which, in the maturation process, are spliced into independent peptides.

The ''pol'' gene codifies for a pol polyprotein containing the protease (PR), reverse transcriptase/ribonuclease H (RT/RNaseH), and integrase (INT) domains. However, PR may also be encoded by a gene alone, as a part of the gag polyprotein, or in frame with a dUTPase domain.

The ''env'' gene codifies for the envelope (env) glycoprotein, which in the maturation process is spliced into the outer surface (SU) membrane protein (the main antigen of the viral envelope), and the transmembrane (TM) protein.

== Morphological types: ==
*Type A particles are unenveloped particles observed only intracellularly; they are most likely noninfectious products of the expression of endogenous retrovirus-like elements.
*Type B particles are enveloped extracellular particles characterized by presenting prominent envelope spikes and an acentric core.
*Type C particles are enveloped extracellular particles characterized by presenting barely visible spikes and a central core.
*Type D particles are enveloped extracellular particles, slightly larger than the other ones and characterized by presenting less prominent spikes.

== Complexity: ==
Vertebrate retroviruses may be divided in simple and complex retroviruses. The main difference between them consists in that while simple retroviruses present the basal LTR-''gag-pol-env''-LTR genomic structure, complex retroviruses incorporate in their genomes some additional accessory genes usually needed to adjust diverse aspects of their replication and infectivity.

== Strategy of transmission: ==
Based on the viral strategy of transmission, retroviruses that enter the germ lines and are vertically transmitted are referred to '''Endogenous Retroviruses (ERVs)''', to distinguish them from horizontally transmitted exogenous retroviruses (for a review in this topic see [[Literature:25672|Gifford and Tristem 2003]]).

== Evolutionary history and viral taxonomy: ==
Consistent with International Committee on the Taxonomy of Viruses (ICTV) ([[Literature:100589|Fauquet ''et al''. 2005]]), the inferred phylogeny of ''Retroviridae'' shows seven genera – ''Alpha-'', ''Beta-'', ''Gamma-'', ''Delta-'', ''Epsilon-'', ''Spumaretrovirus'' and ''Lentivirus''– that together with ERV-L elements we divide into three classes 1, 2 and 3 (according to [[Literature:82792|Wilkinson ''et al.'' 1994]];[[Literature:25671|International Human Genome consortium 2001]]; [[Literature:25671|2002]]; [[Literature:25672|Gifford and Tristem 2003]]; [[Literature:25671|Gifford ''et al.'' 2005]]; [[Literature:93205|Llorens ''et al.'' 2008]]). Class 1 comprises gamma- and epsilonretroviruses; class 2 includes lentiviruses, delta-, alpha- and betaretroviruses; and class 3 encompasses spumaretroviruses and ERV-L elements. Our database also includes an element called ''Snakehead retrovirus'' (SnRV) ([[Literature:29547|Hart ''et al.'' 1996]]), which has unclear classification but that the common LTR retroelement phylogeny places within Class 1 (see, [[Literature:100596|Llorens ''et al''. 2009]]).

In differentiating the ''Retroviridae'' in the three classes 1, 2, and 3, comparative phylogenetic and network analyses reveal a network of relationships whereby class 1 can be related with ''Ty3/Gypsy'' lineages of plants and fungi -such as ''Tat'' and ''Athila'' elements and/or chromoviruses-, class 2 can be related to other ''Ty3/Gypsy'' lineages of insects, such as ''Micropia/Mdg3'' clade; and class 3 with errantiviruses. In light of this polyphyletic scenario we proposed the three kings hypothesis [[Literature:93205|Llorens ''et al.'' 2008]], according to which the three ''Retroviridae'' classes can potentially be tracing three ''Ty3/Gypsy'' ancestors, emerged at different evolutionary times (for more details, see [[Literature:100596|Llorens ''et al''. 2009]]).

{| style="border: 1px solid #000000" cellpadding="4" cellspacing="0" align="center"
|- class="tableHeader"
!Class
!Genus
!Example
!Morphology
|-
|Class 1
|[[Retroviridae#Gammaretrovirus|''Gammaretrovirus'']]
|''Murine Leukemia Virus''
|C-Type
|-
|Class 1
|[[Retroviridae#Epsilonretrovirus|''Epsilonretrovirus'']]
|''Walley Dermal Sarcoma Virus''
| C-Type
|-
|Class 2
|[[Retroviridae#Alpharetroviridae|''Alpharetroviridae'']]
|''Avian Sarcoma and Leukosis Virus''
|C-Type
|-
|Class 2
|[[Retroviridae#Betaretrovirus|''Betaretrovirus'']]
|''Mouse Mammary Tumor Virus''
|B- and D-Type
|-
|Class 2
|[[Retroviridae#Deltaretrovirus|''Deltaretrovirus'']]
|''Bovine Leukemia Virus''
|C-Type
|-
|Class 2
|[[Retroviridae#Lentivirus|''Lentivirus'']]
|''Human Immunodeficiency Virus''
|Cone-shaped core
|-
|Class 3
|[[Retroviridae#Spumaretrovirus|''Spumaretrovirus'']]
|''Human Spumaretrovirus''
|C-Type
|-
|Class 3
|[[Retroviridae#ERV-L|ERV-L]]
|''Murine Endogenous Retrovirus-Leucine''
|A-Type
|}

<center>Taxonomical table summarizing phylogenetic results reported by both [[Phylogeny:GAGPOL_Retroviridae|gag-pol]] and [[Phylogeny:POL_Retroviridae|pol]] ''Retroviridae'' inferred trees</center>

==== Class 1 ====
This class is probably the most ancient branch of vertebrate retroviruses and comprises both gamma- and epsilonretroviruses.
===== ''Gammaretrovirus'' =====
The genus ''Gammaretrovirus'' collects both class 1 endogenous and exogenous C-type retroviruses to which phylogenetic analyses suggest RTVL-I-like viruses and epsilonretroviruses are related. Gammaretroviruses have a simple genome organization consisting in an internal region of 8-9 Kb in size, flanked by LTRs of 0.5 Kb and containing a PBS, ORFs for the ''gag'', ''pol'', and ''env'' genes typically observed in retroviruses, and a PPT adjacent to the 3'LTR.

<center>[[File:Gammaretrovirus.png]]</center>
<center>(''figure not to scale'')</center>

===== ''Epsilonretrovirus'' =====
Epsilonretroviruses describe the C-type class 1 retroviruses of fishes. This genus is represented in this database by the ''Walleye Dermal Sarcoma Virus'' (WDSV) sequence ([[Literature:85423|Martineau ''et al.'' 1991)]]. Phylogenetic analyses suggest that epsilonretroviruses are closely related to gammaretroviruses. However, in difference to gammaretroviruses, WDSV is a complex retrovirus consisting in a full-length genome of 11 Kb in size, flanked by LTRs of 0,9 Kb in size and containing ''gag'', ''pol'', and ''env'' genes, a specific set of [[Accessory Genes|accessory genes]], and also a PPT adjacent to the 3'LTR.

<center>[[File:Epsilonretrovirus.png]]</center>
<center> (''figure not to scale'')</center>

==== Class 2 ====
This class includes alpha-, beta- and deltaretroviruses and lentiviruses.

===== ''Alpharetrovirus'' =====
Alpharetroviruses are C-type class 2 retroviruses comprising both simple and complex retroviruses. Phylogenetic analyses suggest that alpharetroviruses are closely related to betaretroviruses. Alpharetroviruses present an internal region of approximately 6.8-9 Kb in size, flanked by LTRs of 0.3 Kb and characterized by the presence of a PBS, the usual ''gag'', ''pol'' and ''env'' genes of retroviruses, a PPT adjacent to the 3'LTR, and in certain cases one or more [[Accessory Genes|accessory genes]].

<center>[[File:Alpharetrovirus.png]]</center>
<center> (''figure not to scale'')</center>

===== ''Betaretrovirus'' =====
The genus ''Betaretrovirus'' comprises certain class 2 lineages of exogenous and endogenous B- and D-type retroviruses that normally present an internal region of approximately 7.5-9 Kb in size, flanked by LTRs of 0.3-1 Kb, and characterized by the presence of a PBS, a ''gag, dUTPase/pro, pol,'' and ''env'' plus ''OrfX'' genes organization, a PPT adjacent to the 3'LTR, and in certain cases one or more [[Accessory Genes|accessory genes]].

<center>[[File:Betaretrovirus.png]]</center>
<center> (''figure not to scale'')</center>

===== ''Deltaretrovirus'' =====
Deltaretroviruses consist in a group of complex C-type class 2 retroviruses that constitute a well supported cluster along with Alpha- and betaretroviruses. Deltaretroviruses present an internal region of approximately 8-9 Kb in size, flanked by LTRs of 0.7-1 Kb and characterized by the presence of PBS, ORFs for the usual ''gag'', ''pol'', and ''env'' genes of retroviruses, a set of specific [[Accessory Genes|accessory genes]], and also a PPT adjacent to the 3'LTR.

<center>[[File:Deltaretrovirus.png]]</center>
<center>(''figure not to scale'')</center>

===== ''Lentivirus'' =====
Lentiviruses are complex class 2 retroviruses that present an internal region of approximately 8-9 Kb in size, flanked by LTRs of 0,2-1 Kb and characterized by the presence of a PBS, ''gag'', ''pol'', and ''env'' genes, and at least a PPT normally found adjacent to the 3'LTR.
Lentiviruses also codify for a certain number of [[Accessory Genes|accessory genes]] common among all lentiviruses or, in certain cases, exclusively found depending of a clade, a genus, or a particular lentiviral species.

<center>[[File:Lentivirus.png]]</center>
<center>(''figure not to scale'')</center>

==== Class 3 ====
Class 3 encompasses spumaretroviruses and ERV-L elements

===== ''Spumaretrovirus'' =====
Spumaretroviruses are complex C-type class 3 retroviruses whose internal region is approximately 13 Kb in size, flanked by LTRs of 1.7 Kb and characterized by the presence of a PBS, ''gag'', ''pol'' and ''env'' ORFs, a specific set of [[Accessory Genes|accessory genes]], and a PPT adjacent to the 3'LTR.

<center>[[File:Spumaretrovirus.png]]</center>
<center> (''figure not to scale'')</center>

===== ERV-L =====
ERV-L particles are A-type class 3 non-enveloped endogenous elements providing a putative evolutionary intermediate between classical intracellular retrotransposons and infectious retroviruses [[Literature:5608|(Benit ''et al''. 1999)]]. ERV-L elements are represented in this database by the ''Murine Endogenous Retrovirus-Leucine'' (MuERV-L) sequence ([[Literature:5609|Benit ''et al.'' 1997]]). The internal region of this element is 6 Kb in size, flanked by LTRs of 0.5 Kb, and characterized by the presence of a PBS, two ORFs for the ''gag'', and ''pol'' genes typically observed in other LTR retrotransposons and retroviruses, as well as an additional ''dUTPase'' gene downstream to the integrase region, similar to that observed in betaretroviruses and non-primate lentiviruses, and a PPT normally adjacent to the 3'LTR (for more details see [[Element:MuERV-L|MuERV-L]]).
[[Category:Retroelements]]

Retroviridae - Revision history

imported>Gydbwiki at 14:36, 29 April 2010