El VIH comparte con los retrovirus las características esenciales de esa familia. El virión contiene información genética bajo la forma de ácido ribonucléico (ARN), protegido por una envoltura de membrana. Los retrovirus insertan su información genética en las células hospedadora por acción de la transcriptasa inversa.
Un virión del VIH tiene una forma aproximadamente esférica con un diámetro de 80-100 nm. Está constituido por tres capas. La exterior es una bicapa lipídica. Posee 72 prolongaciones formadas por las glicoproteínas gp120 y gp41 que actúan en el momento de la unión del virus a la célula hospedadora. La capa intermedia está constituida por la nucleocápside icosaédrica. la capa interior tiene forma de un cono truncado. Está constituida por el ARN viral y la nucleoproteína. La cadena genética del VIH está constituida por un ARN de cadena simple compuesto por dos filamentos idénticos. El ARN contiene varios genes, cada uno de los cuales codifica las diversas proteínas que el VIH necesita para reproducirse.
Genoma del VIH-1.
Los genomas del VIH-1 y VIH-2 son muy similares. Ambos están compuestos por los tres genes básicos de la familia de los retrovirus. Se trata de los genes gag, pol y env. Cada uno de estos genes codifica proteínas que ayudan a la reproducción del virus. El genoma del VIH posee otros seis genes adicionales: tat, rev, vpu (vpx en el caso del VIH-2), vif y nef.9
Genes estructurales
Las proteínas estructurales son codificadas por los genes gag, pol y env, y su secuencia cubre la mayor parte del genoma viral, quedando sólo una parte menor para el resto de los genes.
El gen gag es traducido a una proteína precursora, la p55, que luego se asocia, durante la gemación por la que se liberan nuevas partículas víricas desde de la célula infectada, a dos copias del ARN viral, para el que presenta una región afín, y a otras proteínas virales y celulares. Una proteasa, producto del gen pol corta durante la maduración del virión la p55 en cuatro proteínas que se incorporan a sus lugares respectivos:
La proteína p24 forma la cápside.
La proteína p17 constituye la matriz, situada bajo la envoltura, a la que estabiliza. Una parte de las proteínas se unen al complejo molecular que acompaña al ADN viral al interior del núcleo. En la superficie de la proteína existe una región cariofílica (literalmente afin al núcleo) que es reconocida por la maquinaria molecular de importación nuclear. Éste es el mecanismo que permite al VIH infectar células diferenciadas, no destinadas a dividirse, algo que no ocurre en ningún otro retrovirus.
Las proteínas p6 y p7 (ó p9) forman la nucleocápside. La región de la p55 correspondiente al polipéptido p6 es responsable de la incorporación de la proteína accesoria Vpr (producto de la traducción del gen vpr) al virión en formación y de la interacción con la membrana de la célula que hace posible la gemación. La p7 (p9) es responsable del reconocimiento y la incorporación del ARN al virión y además interviene en la transcripción inversa facilitándola.
Dentro de la cápside, además de las dos copias idénticas del ARN viral hay ejemplares de tres enzimas necesarias para la multiplicación del virus: una transcriptasa inversa, una integrasa y una proteasa. Estas enzimas, así como una ARNasa se producen a partir de la proteína Pol, después del corte de una proteína precursora mixta derivada de la cotraducción, una de cada 20 veces, de los genes gag y pol. La propia proteasa vírica rompe la proteína anterior, con una eficiencia limitada, para obtener las proteínas Gag (p55) y Pol. Luego la proteína precursora Pol es cortada a su vez para formar las cuatro proteínas funcionales citadas:
La proteasa (p10). Se trata de una aspartil-proteasa cuya forma funcional es un dímero del que se conoce la estructura tridimensional. Actúa cortando las piezas de las proteínas Gag, Pol y de la Gag-Pol. Una parte de los fármacos empleados contra el VIH son inhibidores de su función.
La transcriptasa inversa (p50) cuya función es la síntesis del ADN de doble cadena del provirus usando como patrón la cadena singular del ARN viral. Es una ADN-polimerasa que puede actuar como dependiente del ADN tanto como del ARN. Una vez formada la primera cadena de ADN, complementaria del ARN viral, la ARNasa lo separa de él, lo que permite a la transcriptasa inversa ejecutar la síntesis de la segunda cadena de ADN tomando como molde la primera que se formó. Así pues, para la síntesis de la primera cadena la actividad de la transcriptasa inversa es ARN-dependiente, pero para la de la segunda es ADN-dependiente. También existen múltiples fármacos contra la actividad de la transcriptasa inversa.
La ARNasa (p15), que como se ha dicho separa las cadenas de ARN de las de la ADN durante la transcripción inversa.
La integrasa (p31) realiza la inserción del ADN proviral en el genoma de la célula huésped. No se requiere ATP para su actividad y debe cumplir sucesivamente tres funciones:
Con una actividad exonucleasa corta dos núcleótidos del extremo 3' de cada una de las dos cadenas del ADN proviral.
Con una actividad endonucleasa (de doble cadena) corta el ADN del huésped en el punto de integración. No hay un lugar fijo en el genoma para que esto se realice, sino que ocurre en cualquier región muy accesible de la cromatina, lo que se supone que favorece la expresión del provirus, al coincidir esas regiones del genoma con las más transcritas.
Por último, con una actividad ligasa el ADN proviral es soldado, mediante sólo un enlace covalente en cada extremo, en el ADN celular.
En la actualidad existe un fármaco comercializado contra la actividad de la integrasa, el raltegravir.
La envoltura se basa en una bicapa lipídica, lo mismo que cualquier membrana biológica, y sus componentes estructurales básicos proceden de la membrana plasmática de la célula parasitada. Pero la envoltura porta además regularmente espaciadas 72 espículas, que son complejos proteicos integrados en la membrana formados por proteínas virales codificadas por el gen env. Cada espícula está formada por una pieza de la proteína gp41, integral en la membrana, y una cabeza externa formada por la proteína gp120, esencial para el acoplamiento con el exterior de ciertas células previo a su invasión. Entre los dos componentes de las espículas existe una unión no covalente. Las proteínas gp41 y gp120 se sintetizan como una sola poliproteína, gp160, con la información del gen env antes de que sea cortada por una proteasa de la célula. La proteína Env existe como trímero en la superficie de los viriones y las células infectadas.
Proteínas reguladoras
Tat
La proteína Tat existe en dos formas, una larga, de 101 restos aminoácidos de longitud, y otra más corta, de sólo 72. La segunda se produce cuando en fase temprana se produce una edición completa del ARNm viral, la primera cuando en una fase más tardía sólo se realiza una edición parcial. La proteína Tat (por transactivator) es imprescindible para la producción de nuevos viriones, que promueve activamente. La proteína se une a una región de 59 nucleótidos situada en el extremo 5' del ARN viral llamada TAR (Transactivator Active Region) y actúa como un transactivador, algo excepcional, puesto que éstos suelen unirse al ADN, no al ARN. En cuanto este extremo inicial del genoma viral ha sido transcrito desde el ADN proviral, la proteína Tat se une a él y promueve su elongación favoreciendo la transcripción del resto de la cadena.
Rev
La proteína rev regula la expresión del ARN viral controlando el ritmo de exportación del ARNm.10
Tat y Rev: acción conjunta
La acción sinergística de Tat y Rev fuertemente incrementa la expresión de proteínas virales. Los papeles que Tat y Rev desempeñan en la regulación transcripcional del VIH-1 y en la expresión de proteínas estructurales, respectivamente, hacen Tat y Rev esenciales para el ciclo de vida del VIH. Sus funciones facilitan la expresión de proteínas virales en dos etapas. Después de la integración del ADN proviral y de su transcripción en un nivel basal, solamente los RNAms de 2 KB se transportan al citoplasma. Esto permite la síntesis de Tat, Rev y de Nef. Tat y Rev entonces son transportadas al núcleo, donde actúan para aumentar la transcripción del ADN del provirus (Tat) y del transporte de todos los RNAms virales al citoplasma (Rev). La expresión de proteínas codificada por las clases de RNAm de 9 KB y 4 KB (Gag, Gag-Pol, Env, Vpr, Vif, y de Vpu) puede entonces ocurrir. Estudios donde se han mutado genes virales han determinado que Vif, Vpr, Vpu y Nef no son esenciales para la producción de partículas infecciosas en cultivos celulares in-vitro. Sin embargo, la conservación de dichas proteínas accesorias en el genoma del VIH sugiere que todas desempeñan papeles importantes durante el ciclo infeccioso en el huésped. Los roles de estas proteínas serán descritos a continuación.
Vpu: facilita el desprendimiento de viriones en células infectadas
Vpu es una proteína de 81 aminoácidos que es insertada en membranas vía su terminal nitrogenado. Vpu se acumula en el aparato de Golgi y en endosomas celulares. Vpu es única en HIV-1 y no hay homólogos en lentivirus relacionados como el VIH-2 y el VIS. A Vpu se le han atribuido dos actividades.
Degradación de la proteína CD4
En la ausencia de Vpu, la proteína CD4 interactúa con la proteína viral gp160 recién sintetizada para formar un complejo insoluble, el cual retiene gp120 dentro de la célula. La región citoplásmica de Vpu se puede unir con CD4 y con la proteína β-TrCP. Esto induce la ubiquitinizacion de CD4 y su subsiguiente degradación por el proteasoma, incrementando así la expresión de gp120 en la superficie celular.
Realza en el desprendimiento de viriones de la membrana celular
Esta actividad depende de la región transmembranal de Vpu. En la ausencia de Vpu, los viriones se acumulan en la superficie celular en un estado parcialmente desprendido. Expresión de Vpu resulta en la liberación facilitada de viriones de la membrana celular. Remarcablemente, este efecto no está restringido solamente al VIH-1; Vpu también facilita el desprendimiento de otros virus no relacionados. El mecanismo por la cual esto ocurre es desconocido. Se ha sugerido que Vpu facilita la fluidez de la membrana celular por medio de un canal de cationes. También se ha sugerido que Vpu causa disrupción de interacciones entre proteínas del VIH y de la superficie celular; esto previene la endocitosis de viriones recientemente desprendidos de la célula...
English
The retrovirus HIV shares with the essential characteristics of that family. The virion contains genetic information in the form of ribonucleic acid (RNA), protected by an envelope of membrane. Retroviruses insert their genetic information into host cells by action of reverse transcriptase.
An HIV virion has a roughly spherical shape with a diameter of 80-100 nm. Is constituted by three layers. The exterior is a lipid bilayer. Possesses 72 prolongations formed by glycoproteins gp120 and gp41 that act at the time of virus binding to host cell. The middle layer consists of the icosahedral nucleocapsid. the inner layer has form of a truncated cone. Is constituted by the viral RNA and the nucleoprotein. HIV genetic chain is constituted by a single stranded RNA composed of two identical strands. RNA contains several genes, each of which encodes the various proteins that HIV needs to reproduce.
Genome of HIV-1.
The genomes of HIV-1 and HIV-2 are very similar. Both are composed by the three basic family genes of retroviruses. It is the gag, pol and env. Each of these genes encode proteins that help HIV replication. The HIV genome has six additional genes: tat, rev, vpu (vpx in the case of HIV-2), vif and nef.9
Structural genes
Structural proteins are encoded by genes gag, pol and env, and its sequence covers most viral genome, leaving only a minor part for the rest of genes.
The gag gene is translated into a precursor protein, the p55, which then is associated, during the gemmation by which new virus particles are released from the infected cell, two copies of viral RNA, for which presents an affine region, and other viral and cellular proteins. A protease pol gene product fails during the maturation of the virion protein p55 in four who join their respective places:
The p24 protein forms the capsid.
P17 protein constitutes the matrix, located under the wrapper, which stabilizes. A part of the proteins bind to molecular complex that accompanies the viral DNA into the nucleus. On the surface of the protein there is a region cariofílica (literally akin to the core) that is recognized by the molecular machinery of nuclear import. This is the mechanism that allows HIV to infect differentiated cells, not intended to divide, which does not happen in any other retrovirus.
Proteins p6 and p7 (or p9) form the nucleocapsid. The region of the p55 polypeptide corresponding to p6 is responsible for the incorporation of Vpr accessory protein (product of the vpr gene translation) to virion in formation and interaction with the membrane of the cell that makes possible the budding. The p7 (p9) is responsible for the recognition and incorporation of the virion RNA and also involved in reverse transcription facilitating it.
Inside the capsid, besides the two identical copies of viral RNA are no copies of three enzymes necessary for virus multiplication: a reverse transcriptase, an integrase and a protease. These enzymes, as well as an RNase are produced from the protein Pol, after cutting of a mixed precursor protein derived from the cotraducción, one of every 20 times, of the genes gag and pol. Viral protease itself breaks the previous protein, with a limited efficiency, to obtain the proteins Gag (p55) and Pol Then Pol precursor protein is cut in turn to form the four functional proteins cited:
The protease (p10). This is an aspartyl protease whose functional form is a dimer is known three dimensional structure. Cuts off parts of the proteins Gag, Pol and Gag-Pol. Some of the drugs used against HIV are inhibitors of their function.
Reverse transcriptase (p50) whose function is the synthesis of double-stranded DNA provirus used as singular chain pattern of viral RNA. Is a DNA polymerase which can act as both as DNA-dependent RNA. Once formed the first chain of DNA, complementary viral RNA, RNase separates it from him, allowing reverse transcriptase execute the synthesis of the second DNA strand taking as mold the first that formed. Thus, for the synthesis of the first string the reverse transcriptase activity is RNA-dependent, but for that of the second is DNA-dependent. There are also multiple drugs for reverse transcriptase activity.
RNase (p15), which as said separates the chains of RNA from the DNA during reverse transcription.
Integrase (p31) performs the proviral DNA insertion in the genome of the host cell. ATP is not required for its activity and meet on three functions:
With an exonuclease activity short two nucleotides of 3 'end of each of the two chains proviral DNA.
With an endonuclease activity (double stranded) cuts host DNA in the integration point. There is a fixed location in the genome to make this happen, but occurs in any region very accessible chromatin, which is supposed to favor the expression of the provirus, to match those regions of the genome with the most transcribed.
Finally, with a proviral DNA ligase activity is welded by a covalent bond only at each end, in cellular DNA.
There is now a marketed drug activity against integrase, raltegravir.
The wrapper is basa in a lipid bilayer, the same as any biological membrane, and its basic structural components come from the plasma membrane of the parasitized cell. But besides the wrapper porta 72 regularly spaced spicules, which are protein complexes integrated in the membrane formed by viral proteins encoded by the env gene. Each spicule is formed by a piece of the protein gp41, integral in the membrane, and an outer head formed by the protein gp120, essential for coupling with the outside of certain cells prior to their invasion. Between the two components of spicules exists a noncovalent binding. Gp41 and gp120 proteins are synthesized as a single polyprotein, gp160, with the information of the env gene before it is cut by a protease of the cell. The Env protein exists as trimer on the surface of virions and infected cells.
Regulatory proteins
Tat
Tat protein exists in two forms, a long, of 101 amino acid residues in length, and another shorter, of only 72. The second occurs when there is an early complete edition of the viral mRNA, the first time to a later stage only performed a partial edition. The Tat protein (for transactivator) is essential for the production of new virions, which actively promotes. The protein binds to a region of 59 nucleotides located in the 5 'end of viral RNA called TAR (transactivator Active Region) and acts as a transactivator, something exceptional, since these typically bind DNA, not to RNA. As this initial end of viral genome has been transcribed from the proviral DNA, Tat protein joins him and promotes their elongation favoring the transcription of the rest of the chain.
Rev
Rev protein regulates viral RNA expression controlling the pace of export of ARNm.10
Tat and Rev: joint action
The synergistic action of Tat and Rev strongly increases expression of viral proteins. The roles that Tat and Rev play in transcriptional regulation of HIV-1 and in the expression of structural proteins, respectively, make Tat and Rev essential for the HIV life cycle. Their functions facilitate the expression of viral proteins in two stages. After proviral DNA integration and its transcription in a basal level, only the RNAms of 2 KB are transported to the cytoplasm. This allows the synthesis of Tat, Rev and Nef. Tat and Rev are then transported to the nucleus where they act to increase transcription of the provirus DNA (Tat) and transport of all viral RNAms the cytoplasm (Rev). The expression of proteins encoded by the mRNA classes 9 KB and 4 KB (Gag, Gag-Pol, Env, Vpr, Vif, and Vpu) can then occur. Studies that have mutated viral genes have determined that Vif, Vpr, Vpu and Nef are not essential for the production of infectious particles in cell cultures in vitro. However, the conservation of such accessory proteins in the HIV genome suggests that all play important roles during the infectious cycle in the host. The roles of these proteins will be described below.
Vpu: facilitates the detachment of virions in infected cells
Vpu is a protein of 81 amino acids that is inserted into membranes via its terminal nitrogen. Vpu is accumulated in the Golgi apparatus and cell endosomes. Vpu is unique in HIV-1 and no homologs in related lentiviruses like HIV-2 and VIS. A Vpu have been attributed to two activities.
CD4 protein degradation
In the absence of Vpu, the CD4 protein interacts with newly synthesized viral protein gp160 to form an insoluble complex, which retains gp120 within the cell. The cytoplasmic region of Vpu can bind with CD4 and β-TrCP protein. This induces the ubiquitination of CD4 and its subsequent degradation by the proteasome, thereby increasing the expression of gp120 in the cell surface.
Enhances in detachment of virions from the cell membrane
This activity depends on the transmembrane region of Vpu. In the absence of Vpu, virions accumulate in the cell surface in a partially detached. Vpu expression results in release of virions facilitated cell membrane. Remarkably, this effect is not restricted only to HIV-1, Vpu also facilitates the release of other unrelated viruses. The mechanism by which this occurs is unknown. It has been suggested that Vpu facilitates the cellular membrane fluidity through a cation channel. Also been suggested that Vpu cause disruption of interactions between HIV proteins and cell surface; this prevents endocytosis of virions recently detached from the cell ...
An HIV virion has a roughly spherical shape with a diameter of 80-100 nm. Is constituted by three layers. The exterior is a lipid bilayer. Possesses 72 prolongations formed by glycoproteins gp120 and gp41 that act at the time of virus binding to host cell. The middle layer consists of the icosahedral nucleocapsid. the inner layer has form of a truncated cone. Is constituted by the viral RNA and the nucleoprotein. HIV genetic chain is constituted by a single stranded RNA composed of two identical strands. RNA contains several genes, each of which encodes the various proteins that HIV needs to reproduce.
Genome of HIV-1.
The genomes of HIV-1 and HIV-2 are very similar. Both are composed by the three basic family genes of retroviruses. It is the gag, pol and env. Each of these genes encode proteins that help HIV replication. The HIV genome has six additional genes: tat, rev, vpu (vpx in the case of HIV-2), vif and nef.9
Structural genes
Structural proteins are encoded by genes gag, pol and env, and its sequence covers most viral genome, leaving only a minor part for the rest of genes.
The gag gene is translated into a precursor protein, the p55, which then is associated, during the gemmation by which new virus particles are released from the infected cell, two copies of viral RNA, for which presents an affine region, and other viral and cellular proteins. A protease pol gene product fails during the maturation of the virion protein p55 in four who join their respective places:
The p24 protein forms the capsid.
P17 protein constitutes the matrix, located under the wrapper, which stabilizes. A part of the proteins bind to molecular complex that accompanies the viral DNA into the nucleus. On the surface of the protein there is a region cariofílica (literally akin to the core) that is recognized by the molecular machinery of nuclear import. This is the mechanism that allows HIV to infect differentiated cells, not intended to divide, which does not happen in any other retrovirus.
Proteins p6 and p7 (or p9) form the nucleocapsid. The region of the p55 polypeptide corresponding to p6 is responsible for the incorporation of Vpr accessory protein (product of the vpr gene translation) to virion in formation and interaction with the membrane of the cell that makes possible the budding. The p7 (p9) is responsible for the recognition and incorporation of the virion RNA and also involved in reverse transcription facilitating it.
Inside the capsid, besides the two identical copies of viral RNA are no copies of three enzymes necessary for virus multiplication: a reverse transcriptase, an integrase and a protease. These enzymes, as well as an RNase are produced from the protein Pol, after cutting of a mixed precursor protein derived from the cotraducción, one of every 20 times, of the genes gag and pol. Viral protease itself breaks the previous protein, with a limited efficiency, to obtain the proteins Gag (p55) and Pol Then Pol precursor protein is cut in turn to form the four functional proteins cited:
The protease (p10). This is an aspartyl protease whose functional form is a dimer is known three dimensional structure. Cuts off parts of the proteins Gag, Pol and Gag-Pol. Some of the drugs used against HIV are inhibitors of their function.
Reverse transcriptase (p50) whose function is the synthesis of double-stranded DNA provirus used as singular chain pattern of viral RNA. Is a DNA polymerase which can act as both as DNA-dependent RNA. Once formed the first chain of DNA, complementary viral RNA, RNase separates it from him, allowing reverse transcriptase execute the synthesis of the second DNA strand taking as mold the first that formed. Thus, for the synthesis of the first string the reverse transcriptase activity is RNA-dependent, but for that of the second is DNA-dependent. There are also multiple drugs for reverse transcriptase activity.
RNase (p15), which as said separates the chains of RNA from the DNA during reverse transcription.
Integrase (p31) performs the proviral DNA insertion in the genome of the host cell. ATP is not required for its activity and meet on three functions:
With an exonuclease activity short two nucleotides of 3 'end of each of the two chains proviral DNA.
With an endonuclease activity (double stranded) cuts host DNA in the integration point. There is a fixed location in the genome to make this happen, but occurs in any region very accessible chromatin, which is supposed to favor the expression of the provirus, to match those regions of the genome with the most transcribed.
Finally, with a proviral DNA ligase activity is welded by a covalent bond only at each end, in cellular DNA.
There is now a marketed drug activity against integrase, raltegravir.
The wrapper is basa in a lipid bilayer, the same as any biological membrane, and its basic structural components come from the plasma membrane of the parasitized cell. But besides the wrapper porta 72 regularly spaced spicules, which are protein complexes integrated in the membrane formed by viral proteins encoded by the env gene. Each spicule is formed by a piece of the protein gp41, integral in the membrane, and an outer head formed by the protein gp120, essential for coupling with the outside of certain cells prior to their invasion. Between the two components of spicules exists a noncovalent binding. Gp41 and gp120 proteins are synthesized as a single polyprotein, gp160, with the information of the env gene before it is cut by a protease of the cell. The Env protein exists as trimer on the surface of virions and infected cells.
Regulatory proteins
Tat
Tat protein exists in two forms, a long, of 101 amino acid residues in length, and another shorter, of only 72. The second occurs when there is an early complete edition of the viral mRNA, the first time to a later stage only performed a partial edition. The Tat protein (for transactivator) is essential for the production of new virions, which actively promotes. The protein binds to a region of 59 nucleotides located in the 5 'end of viral RNA called TAR (transactivator Active Region) and acts as a transactivator, something exceptional, since these typically bind DNA, not to RNA. As this initial end of viral genome has been transcribed from the proviral DNA, Tat protein joins him and promotes their elongation favoring the transcription of the rest of the chain.
Rev
Rev protein regulates viral RNA expression controlling the pace of export of ARNm.10
Tat and Rev: joint action
The synergistic action of Tat and Rev strongly increases expression of viral proteins. The roles that Tat and Rev play in transcriptional regulation of HIV-1 and in the expression of structural proteins, respectively, make Tat and Rev essential for the HIV life cycle. Their functions facilitate the expression of viral proteins in two stages. After proviral DNA integration and its transcription in a basal level, only the RNAms of 2 KB are transported to the cytoplasm. This allows the synthesis of Tat, Rev and Nef. Tat and Rev are then transported to the nucleus where they act to increase transcription of the provirus DNA (Tat) and transport of all viral RNAms the cytoplasm (Rev). The expression of proteins encoded by the mRNA classes 9 KB and 4 KB (Gag, Gag-Pol, Env, Vpr, Vif, and Vpu) can then occur. Studies that have mutated viral genes have determined that Vif, Vpr, Vpu and Nef are not essential for the production of infectious particles in cell cultures in vitro. However, the conservation of such accessory proteins in the HIV genome suggests that all play important roles during the infectious cycle in the host. The roles of these proteins will be described below.
Vpu: facilitates the detachment of virions in infected cells
Vpu is a protein of 81 amino acids that is inserted into membranes via its terminal nitrogen. Vpu is accumulated in the Golgi apparatus and cell endosomes. Vpu is unique in HIV-1 and no homologs in related lentiviruses like HIV-2 and VIS. A Vpu have been attributed to two activities.
CD4 protein degradation
In the absence of Vpu, the CD4 protein interacts with newly synthesized viral protein gp160 to form an insoluble complex, which retains gp120 within the cell. The cytoplasmic region of Vpu can bind with CD4 and β-TrCP protein. This induces the ubiquitination of CD4 and its subsequent degradation by the proteasome, thereby increasing the expression of gp120 in the cell surface.
Enhances in detachment of virions from the cell membrane
This activity depends on the transmembrane region of Vpu. In the absence of Vpu, virions accumulate in the cell surface in a partially detached. Vpu expression results in release of virions facilitated cell membrane. Remarkably, this effect is not restricted only to HIV-1, Vpu also facilitates the release of other unrelated viruses. The mechanism by which this occurs is unknown. It has been suggested that Vpu facilitates the cellular membrane fluidity through a cation channel. Also been suggested that Vpu cause disruption of interactions between HIV proteins and cell surface; this prevents endocytosis of virions recently detached from the cell ...
No hay comentarios:
Publicar un comentario