structure of retrovirus

7/23/2019 Structure of Retrovirus

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Structure of retrovirus

Virionsof retroviruses consist of enveloped particles about 100 nm in diameter. The virions also contain two

identical single-stranded RNAmolecules 710 !ilobasesin length. Although virions of different retroviruses do not

have the same morpholog" or biolog"# all the virion components are ver" similar.$%&

The main virion components are'

(nvelope' composed of lipids )obtained from the hostplasma membraneduring budding process* as well as

gl"coprotein encoded b" the env gene. The retroviral envelope serves three distinct functions' protection from

the e+tracellular environment via the lipid bila"er# enabling the retrovirus to enter,e+it host cells through

endosomal membrane traffic!ing# and the abilit" to directl" enter cells b" fusing with their membranes.

RNA' consists of a dimerRNA. t has a cap at the / end and a pol")A* tail at the / end. The RNA genome

also has terminal noncoding regions# which are important in replication# and internal regions that encode virion

proteins for gene e+pression. The / end includes four regions# which are R# # 234# and 5. The R region is a

short repeated se6uence at each end of the genome used during thereverse transcriptionto ensure correctend-to-end transfer in the growing chain. # on the other hand# is a short uni6ue se6uence between R and

234. 234 )primer binding site* consists of 1 bases complementar" to / end of tRNA primer. 5 region is an

untranslated leader region that gives the signal for pac!aging of the genome RNA. The / end includes

regions# which are 22T )pol"purine tract*# # and R. The 22T is a primer for plus-strand 8NA s"nthesis

during reverse transcription. is a se6uence between 22T and R# which serves as a signal that the provirus

can use in transcription.R is the terminal repeated se6uence at / end.

2roteins' consisting of gag proteins# protease)2R*# pol proteins# and env proteins.

9roup-specific antigen)gag* proteins are ma:or components of the viralcapsid# which are about

%000;000 copies per virion.

2rotease is e+pressed differentl" in different viruses. t functions in proteol"tic cleavages during

virion maturation to ma!e mature gag and pol proteins.

2ol proteins are responsible for s"nthesis of viral 8NA and integration into host 8NA after infection.

(nv proteins pla" a role in association and entr" of virions into the host cell.$&2ossessing a

functional cop" of an env geneis what ma!es retroviruses distinct from retroelements. $;&The abilit" of theretrovirus to bind to its target host cell using specific cell-surface receptors is given b" the surface

component )4* of the (nv protein# while the abilit" of the retrovirus to enter the cell via membrane fusion is

imparted b" the membrane-anchored trans-membrane component )T


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base-paired duple+ with the viral RNA at 234. The fact that the 234 is located near the = terminus of viral

RNA is unusual because reverse transcriptase s"nthesi>e 8NA from = end of the primer in the = to =

direction )with respect to the RNA template*.Therefore# the primer and reverse transcriptase must be

relocated to = end of viral RNA. n order to accomplish this reposition# multiple steps and various en>"mes

including8NA pol"merase#ribonuclease ?)RNase ?* and pol"nucleotide unwinding are needed. $@&

The ?V reverse transcriptase also hasribonucleaseactivit" that degrades the viral RNA during the

s"nthesis of c8NA# as well as 8NA-dependent 8NA pol"meraseactivit" that copies the sensec8NA strand

into an antisense8NA to form a double-stranded viral 8NA intermediate )v8NA*.$

Retroviral reverse transcription[edit]

Retroviruses# also referred to as class V ssRNA-RTviruses# are RNA reverse transcribing viruses with a 8NA

intermediate. Their genomes consist of two molecules of positive-sensesingle stranded RNA with a / capand /

pol"aden"lated tail. (+amples of retroviruses include the human immunodeficienc" virus )?V* and the human T-

l"mphotropic virus )?T5V*. reation of double-stranded 8NA occurs in thec"tosol$7&as a series of these steps'

1. A specific cellulartRNAacts as a primer and h"bridi>es to a complementar" part of the virus RNA genome

called the primer binding site or 234
https://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-isbn0-87969-167-0-9https://en.wikipedia.org/wiki/Ribonucleasehttps://en.wikipedia.org/wiki/Ribonucleasehttps://en.wikipedia.org/wiki/DNA-dependent_DNA_polymerasehttps://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-10https://en.wikipedia.org/w/index.php?title=Reverse_transcriptase&action=edit&section=4https://en.wikipedia.org/w/index.php?title=Reverse_transcriptase&action=edit&section=4https://en.wikipedia.org/w/index.php?title=Reverse_transcriptase&action=edit&section=4https://en.wikipedia.org/wiki/Retroviruseshttps://en.wikipedia.org/wiki/SsRNA-RThttps://en.wikipedia.org/wiki/Sense_(molecular_biology)#RNA_sense_in_viruseshttps://en.wikipedia.org/wiki/5'_caphttps://en.wikipedia.org/wiki/Polyadenylationhttps://en.wikipedia.org/wiki/Polyadenylationhttps://en.wikipedia.org/wiki/HIVhttps://en.wikipedia.org/wiki/HTLVhttps://en.wikipedia.org/wiki/Cytosolhttps://en.wikipedia.org/wiki/Cytosolhttps://en.wikipedia.org/wiki/Cytosolhttps://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-7https://en.wikipedia.org/wiki/TRNAhttps://en.wikipedia.org/wiki/TRNAhttps://en.wikipedia.org/wiki/DNA_polymerasehttps://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-isbn0-87969-167-0-9https://en.wikipedia.org/wiki/Ribonucleasehttps://en.wikipedia.org/wiki/DNA-dependent_DNA_polymerasehttps://en.wikipedia.org/wiki/Sense_(molecular_biology)https://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-10https://en.wikipedia.org/w/index.php?title=Reverse_transcriptase&action=edit&section=4https://en.wikipedia.org/wiki/Retroviruseshttps://en.wikipedia.org/wiki/SsRNA-RThttps://en.wikipedia.org/wiki/Sense_(molecular_biology)#RNA_sense_in_viruseshttps://en.wikipedia.org/wiki/5'_caphttps://en.wikipedia.org/wiki/Polyadenylationhttps://en.wikipedia.org/wiki/Polyadenylationhttps://en.wikipedia.org/wiki/HIVhttps://en.wikipedia.org/wiki/HTLVhttps://en.wikipedia.org/wiki/Cytosolhttps://en.wikipedia.org/wiki/Reverse_transcriptase#cite_note-7https://en.wikipedia.org/wiki/TRNA


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%. omplementar" 8NAthen binds to the )non-coding region* and R region )a direct repeat found at both

ends of the RNA molecule* of the viral RNA

. A domain on the reverse transcriptase en>"me called RNAse ?degrades the = end of the RNA which

removes the and R region

;. The primer then B:umps= to the = end of the viral genome and the newl" s"nthesised 8NA strands h"bridi>es

to the complementar" R region on the RNA

. The first strand of complementar" 8NA )c8NA* is e+tended and the ma:orit" of viral RNA is degraded b"

RNAse ?

C. Dnce the strand is completed# second strand s"nthesis is initiated from the viral RNA

7. There is then another B:ump= where the 234 from the second strand h"bridi>es with the complementar" 234

on the first strand

. 3oth strands are e+tended further and can be incorporated into the hosts genome b" the en>"me integrase

reation of double-stranded 8NA also involves strand transfer# in which there is a translocation of short 8NA

product from initial RNA dependent 8NA s"nthesis to acceptor template regions at the other end of the genome#

which are later reached and processed b" the reverse transcriptase for its 8NA-dependent 8NA activit"

A Reverse transcriptase)RT* is anen>"meused to generate complementar" 8NA)c8NA* from anRNAtemplate#

a process termed reverse transcription. t is mainl" associated with retroviruses.t should be noted however that

also non-retroviruses use RT )for e+ample# the hepatitis 3 virus#a member of the?epadnaviridae# which

are ds8NA-RT viruses# while retroviruses are ssRNA viruses*. RT inhibitors are widel" used as antiretroviral drugs.

RT activities are also associated with the replication of chromosome ends )telomerase* and some mobile genetic

elements )retrotransposons*.

Retroviral RT has three se6uential biochemical activities'

)a* RNA-dependent 8NA pol"merase activit"#

)b* ribonuclease ?# and

)c* 8NA-dependent 8NA pol"merase activit".

These activities are used b" the retrovirus to convert single-stranded genomic RNA into double-stranded c8NA

which can integrate into the host genome# potentiall" generating a long-term infection that can be ver" difficult to

eradicate. The same se6uence of reactions is widel" used in the laborator" to convert RNA to 8NA for use

in molecular cloning# RNA se6uencing# pol"merase chain reaction)2R*# orgenome anal"sis.

Reverse transcriptases were discovered b" ?oward Teminat the niversit" of Eisconsin


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againR4V.$&For their achievements# both shared the 1@7 Nobel 2ri>e in 2h"siolog" or "mes )2ol# pol"merase* or the

gl"coproteins of the virion env)envelope*.$1C&n addition to these# ?V encodes for proteins which have certain

regulator" and au+iliar" functions as well. $1C&?V-1 has two important regulator" elements' Tat and Rev and few

important accessor" proteins such as Nef# Vpr# Vif and Vpu which are not essential for replication in certain tissues.

$17&The gaggene provides the basic ph"sical infrastructure of the virus# andpolprovides the basic mechanism b"

which retroviruses reproduce# while the others help ?V to enter the host cell and enhance its reproduction. Though

the" ma" be altered b" mutation# all of these genes e+cept teve+ist in all !nown variants of ?VH

?V emplo"s a sophisticated s"stem of differentialRNA splicingto obtain nine different gene products from a less

than 10!b genome.$1&?V has a @.%!b unspliced genomic transcript which encodes for gag and pol precursorsH a

singl" spliced# ;. !b encoding for env# Vif# Vpr and Vpu and a multipl" spliced# % !b mRNA encoding for Tat# Rev

and Nef.$1&

Proteins encoded by the HIV genoe

C!ass Gene nae Priary protein prod"cts Processed protein prod"cts

Viral structural proteins gag 9ag pol"protein


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pol 2ol pol"protein RT# RNase ?# N# 2R

env gp1C0 gp1%0# gp;1

(ssential regulator" elements tat Tat

rev Rev

Accessor" regulator" proteins nef Nef

vpr Vpr

vif Vif

vpu Vpu

Vira! str"ct"ra! proteins

gag)group-specific antigen* codes for the precursor gagpol"proteinwhich is processed b" viral proteaseduring maturation to "mes reverse transcriptase)RT* and RNase ?# integrase)N*# and?V protease)2R*.

$1C&?V protease is re6uired to cleave the precursor 9ag pol"protein to produce structural proteins# RT is

re6uired to transcribe 8NA from RNA template# and N is necessar" to integrate the double-stranded viral 8NA

into the host genome.$1&

env)for GenvelopeG* codes for gp1C0#which is cleaved b" a host protease# furin#within theendoplasmic

reticulumof the host cell. The post-translational processing produces a surface gl"coprotein#gp1%0or 4#

which attaches to the 8;receptors present on l"mphoc"tes# andgp;1or T


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important role earl" in ?V infection. Tat )1;-1!8a* binds to the bulged genomic RNA stem-loopsecondar"

structure near the / 5TR region forming the trans-activation response element )TAR*.$&$1C&

rev)regulator of e+pression of virion proteins*' The Rev protein binds to the viral genome via an arginine-rich

RNA-binding motif that also acts as a N54 )nuclear locali>ation signals*# re6uired for the transport of Rev to the

nucleus from c"tosol during viral replication. $1C&Rev recogni>es a comple+ stem-loop structure of the

mRNA envlocated in the intron separating coding e+on of Tat and Rev# !nown as the?V Rev response

element)RR(*.$&$1C&Rev is important for the s"nthesis of ma:or viral proteins and is hence essential for viral

replication.

#ccessory reg"!atory proteins$edit&

vpr)lentivirusprotein R*' Vpr is a virion-associated# nucleoc"toplasmic shuttling regulator" protein.$1C&t is

believed to pla" an important role in replication of the virus# specificall"# nuclear import of the preintegration

comple+. Vpr also appears to cause its host cells to arrest their cell c"clein the 9% phase. This arrest activates

the host 8NA repair machiner" which ma" enable integration of the viral 8NA.$&?V-%and4Vencode an

additional Vpr related protein called Vp+ which functions in association with Vpr.$1C&

vif- Vif is a highl" conserved# % !8a phosphoprotein important for the infectivit" of ?V-1 virions depending

on the cell t"pe.$&?V-1 has been found to re6uire Vif to s"nthesi>e infectious viruses in l"mphoc"tes#

macrophages# and certain human cell lines. t does not appear to re6uire Vif for the same process in ?e5acells

orD4 cells#among others.$1C&

nef- Nef# negative factor# is a N-terminal m"risto"lated membrane-associated phosphoprotein. t is involved

in multiple functions during the replication c"cle of the virus. t is believed to pla" an important role in cell

apoptosis and increase in virus infectivit".$1C&

vpu)Virus protein * - Vpu is specific to ?V-1. t is a class oligomeric integral membrane phosphoprotein

with numerous biological functions. Vpu is involved in 8;degradation involving the

ubi6uitin proteasomepathwa" as well as in the successful release of virions from infected cells. $&$1C&

tev' This gene is onl" present in a few ?V-1 isolates. t is a fusion of parts of the tat# env# and revgenes#

and codes for a protein with some of the properties of tat# but little or none of the properties of rev

he h"an i"node$iciency vir"s %HIV&'

?V belongs to a group of retroviruses called lentiviruses. The genome of retroviruses is made

of RNA )ribonucleic acid*# and each virus has two sing!e chainsof RNAH for replication# thevirus needs a host cell# and the RNA must first be transcribed into 8NA )deo+"ribonucleicacid*# which is done with the en>"me reverse transcriptase.

?V infects mainl" the 8;I l"mphoc"tes )T cells*# but also to a lesser degree monoc"tes#macrophages# and dendritic cells )these cells are also 8;I cells*. Dnce infected# the cellturns into an ?V-replicating cell and loses its function in the human immune s"stem.
https://en.wikipedia.org/wiki/Stem-loophttps://en.wikipedia.org/wiki/Stem-loophttps://en.wikipedia.org/wiki/Trans-activation_response_element_(TAR)https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Rev_(HIV)https://en.wikipedia.org/wiki/Argininehttps://en.wikipedia.org/wiki/Nuclear_localization_signalhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/HIV_Rev_response_elementhttps://en.wikipedia.org/wiki/HIV_Rev_response_elementhttps://en.wikipedia.org/wiki/HIV_Rev_response_elementhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/w/index.php?title=Structure_and_genome_of_HIV&action=edit&section=5https://en.wikipedia.org/wiki/Vprhttps://en.wikipedia.org/wiki/Lentivirushttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Cell_cyclehttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/HIV-2https://en.wikipedia.org/wiki/Simian_immunodeficiency_virushttps://en.wikipedia.org/wiki/Simian_immunodeficiency_virushttps://en.wikipedia.org/wiki/Simian_immunodeficiency_virushttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Viral_infectivity_factorhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/HeLahttps://en.wikipedia.org/wiki/COS_cellshttps://en.wikipedia.org/wiki/COS_cellshttps://en.wikipedia.org/wiki/COS_cellshttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Nef_(protein)https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Vpuhttps://en.wikipedia.org/wiki/CD4https://en.wikipedia.org/wiki/Proteasomehttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Tat_(HIV)https://en.wikipedia.org/wiki/Regulator_of_Virionhttps://en.wikipedia.org/wiki/Stem-loophttps://en.wikipedia.org/wiki/Trans-activation_response_element_(TAR)https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Rev_(HIV)https://en.wikipedia.org/wiki/Argininehttps://en.wikipedia.org/wiki/Nuclear_localization_signalhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/HIV_Rev_response_elementhttps://en.wikipedia.org/wiki/HIV_Rev_response_elementhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/w/index.php?title=Structure_and_genome_of_HIV&action=edit&section=5https://en.wikipedia.org/wiki/Vprhttps://en.wikipedia.org/wiki/Lentivirushttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Cell_cyclehttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/HIV-2https://en.wikipedia.org/wiki/Simian_immunodeficiency_virushttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Viral_infectivity_factorhttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/HeLahttps://en.wikipedia.org/wiki/COS_cellshttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Nef_(protein)https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Vpuhttps://en.wikipedia.org/wiki/CD4https://en.wikipedia.org/wiki/Proteasomehttps://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Montagnier.2C_Luc_1999-5https://en.wikipedia.org/wiki/Structure_and_genome_of_HIV#cite_note-Votteler.2C_J_2008-16https://en.wikipedia.org/wiki/Tat_(HIV)https://en.wikipedia.org/wiki/Regulator_of_Virion


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HIV str"ct"re'

An ?V virus particle is spherical andhas a diameter of about 1,10#000mm.

5i!e other viruses# ?V does not

have a cell wall or a nucleus.

The basic structure of the virus is as follows' - The vira! enve!ope# the outer coat of the virus# consists of two la"ers of lipidsH different

proteins are embedded in the viral envelope# forming Gspi!esG consisting of theouter g!ycoprotein %gp& ()*and the transmembrane gp+(. The lipid membrane is borrowedfrom the host cell during the budding process )formation of new particles*. gp1%0 is needed toattach to the host cell# and gp;1 is critical for the cell fusion process.

- The HIV atri, proteins %consisting o$ the p(- protein& # lie between the envelope andcore.

- The vira! core# contains the viral capsule protein p)+which surrounds two single strands of?V RNA and the en>"mes needed for ?V replication# such as reverse transcriptase#protease# ribonuclease# and integraseH out of the nine virus genes# there are three# namel"gag# pol and env# that contain the information needed to ma!e structural proteins for new virusparticles.

HIV sequence database

DATABASES

SEARCH

ALIGNMENTS

TOOLS
http://www.hiv.lanl.gov/content/indexhttp://www.hiv.lanl.gov/components/sequence/HIV/search/search.htmlhttp://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.htmlhttp://www.hiv.lanl.gov/content/sequence/HIV/HIVTools.htmlhttp://www.hiv.lanl.gov/content/indexhttp://www.hiv.lanl.gov/components/sequence/HIV/search/search.htmlhttp://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.htmlhttp://www.hiv.lanl.gov/content/sequence/HIV/HIVTools.html


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PUBLICATIONS

GUIDES

HIV-1 Gene Ma

Land!a"#s $% t&e HIV-1 'en$!e( H)B* +,./002Open reading frames are shown as rectangles.

The gene start, indicated by the small number in the upper left corner of each rectangle, normally

records the position of the a in the ATG start codon for that gene, while the number in the lower

right records the last position of the stop codon. For pol, the start is taken to be the first T in the

sequence TTTTTTAG, which forms part of the stem loop that potentiates ribosomal slippage on the

RA and a resulting !" frameshift and the translation of the Gag!#ol polyprotein. The tat and re$

spliced e%ons are shown as shaded rectangles. &n '()*, +--* marks position of frameshift in the

$pr gene caused by an e%tra T relati$e to most other subtype ) $iruses/ 0121* indicates a

defecti$e A3G start codon in $pu/ 456*6, and 47"15 mark premature stop codons in tat and nef. 8ee

9orber et al., umbering #ositions in '&: Relati$e to '()*3G, in the database compendium, Human

Retroviruses and AIDS, "775.

Annotation Resources

8preadsheets with in!depth annotation of genome features and coordinates are a$ailable; &n!depth

Annotation Resources.

Genes and Gene #roducts

GAGThe genomic region encoding the capsid proteins


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POLThe genomic region encoding the $iral enymes protease, re$erse transcriptase, and integrase.

These enymes are produced as a Gag!#ol precursor polyprotein, which is processed by the $iral

protease/ the Gag!#ol precursor is produced by ribosome frameshifting near the BC end ofgag.

ENV:iral glycoproteins produced as a precursor @#?F

REVThe second necessary regulatory factor for '&: e%pression. A "7!k? phosphoprotein, localied

primarily in the nucleolusEnucleus, Re$ acts by binding to RR and promoting the nuclear e%port,

stabiliation, and utiliation of the $iral mRAs containing RR. Re$ is considered the most

functionally conser$ed regulatory protein of lenti$iruses. Re$ cycles rapidly between the nucleus

and the cytoplasm.

VI3:iral infecti$ity factor, a basic protein typically *B k?. #romotes the infecti$ity but not the

production of $iral particles. &n the absence of :if, the produced $iral particles are defecti$e, while

the cell!to!cell transmission of $irus is not affected significantly. Found in almost all lenti$iruses,

:if is a cytoplasmic protein, e%isting in both a soluble cytosolic form and a membrane!associated

form. The latter form of :if is a peripheral membrane protein that is tightly associated with the

cytoplasmic side of cellular membranes. &n *22B, it was disco$ered that :if pre$ents the action of

the cellular A#O)3!BG protein, which deaminates ?A;RA heteroduple%es in the cytoplasm. Read

re$iew article; #?F

VPR:pr >, or other 8&:s. :pu is a "1!kd


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:pu probably possesses an !terminal hydrophobic membrane anchor and a hydrophilic moiety. &t is

phosphorylated by casein kinase && at positions 8er* and 8er1. :pu is in$ol$ed in n$ maturation

and is not found in the $irion. :pu has been found to increase susceptibility of '&:!" infected cells

to Fas killing.

NE3A multifunctional *-!kd myristoylated protein produced by an ORF located at the BC end of the

primate lenti$iruses. Other forms of ef are known, including nonmyristoylated $ariants. ef is

predominantly cytoplasmic and associated with the plasma membrane $ia the myristoyl residue

linked to the conser$ed second amino acid >, 8&:!R3>, 8&:!>?!*, and 8&:!?R@ and not in

'&:!" or other 8&:s. This accessory gene is a homolog of '&:!" $pr, and $iruses with $p% carry both

$pr and $p%. :p% function in relation to :pr is not fully elucidated/ both are incorporated into

$irions at le$els comparable to Gag proteins through interactions with Gag p1. :p% is necessary for

efficient replication of 8&:!8>> in #)>3s. #rogression to A&?8 and death in 8&:!infected animals can

occur in the absence of :pr or :p%. ?ouble mutant $irus lacking both $pr and $p% was attenuated,

whereas the single mutants were not, suggesting a redundancy in the function of :pr and :p%

related to $irus pathogenicity.

'&: Genomic 8tructural lements

LTR@ong terminal repeat, the ?A sequence flanking the genome of integrated pro$iruses. &t

contains important regulatory regions, especially those for transcription initiation and

polyadenylation. Read re$iew article; 'T>@#?F

TARTarget sequence for $iral transacti$ation, the binding site for Tat protein and for cellular

proteins/ consists of appro%imately the first 6 nucleotides of the $iral mRAs in '&:!"


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is the binding site for Re$ protein, while R(R is the binding site for Re% protein. RR ishra et al.

*221for structural information about RR.

PE#si elements, a set of 6 stem!loop structures preceding and o$erlapping the Gag start codon. #

are the sites recognied by the cysteine histidine bo%, a conser$ed motif with the canonical

sequence 3ys(*3ys(6'is(63ys, present in the Gag p- 3 protein. The #si lements are present in

unspliced genomic transcripts, but absent from spliced $iral mRAs.

SLIPA TTTTTT slippery site, followed by a stem!loop structure, is responsible for regulating the !"

ribosomal frameshift out of the Gag reading frame into the #ol reading frame.

CRS3is!acting repressi$e sequences postulated to inhibit structural protein e%pression in theabsence of Re$. One such site was mapped within the pol region of '&:!". The e%act function has

not been defined/ splice sites ha$e been postulated to act as 3R8 sequences.

INS&nhibitoryE&nstability RA sequences found within the structural genes of '&:!" and of other

comple% retro$iruses. >ultiple &8 elements e%ist within the genome and can act independently/

one of the best characteried elements spans nucleotides 6"6 to 1B" in thegag region of '&:!". The&8 elements ha$e been defined by functional assays as elements that inhibit e%pression

posttranscriptionally. >utation of the RA elements was shown to lead to &8 inacti$ation and up!

regulation of gene e%pression.

STRUCTURAL PROTEINS4VIRAL EN56MESThe products ofgag,pol, and env genes, which are

essential components of the retro$iral particle.

REGULATOR6 PROTEINSTat and Re$ proteins of '&:E8&: and Ta% and Re% proteins of 'T@:s. They

modulate transcriptional and posttranscriptional steps of $irus gene e%pression and are essentialfor $irus propagation.

ACCESSOR6 OR AU)ILIAR6 PROTEINSAdditional $irion and non!$irion!associated proteins produced

by '&:E8&: retro$iruses; :if, :pr, :pu, :p%, ef. Although the accessory proteins are in general not

necessary for $iral propagation in tissue culture, they ha$e been conser$ed in the different

isolates/ this conser$ation and e%perimental obser$ations suggest that their role in vivois $ery

important. Their functional importance continues to be elucidated.

COMPLE) RETROVIRUSESRetro$iruses regulating their e%pression $ia $iral factors and e%pressing

additional proteins


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structure of retrovirus

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