New Approaches in HIV Management- Part 2
April 23rd 2011 11:24
Blocking the Entry of HIV into Cells
The first step in HIV infection of a host cell is to get into its cytosol. This is done by attachment of HIV to a cell’s CD4 receptor via its gp 120 protein coat. Once CD$-gp 120 complex is established, gp 120 undergoes conformational change that facilitates binding to one of a group of co-receptors (CCR5 and CXCR4). Trhis event establishes fusion of the virus into a host’s membrane, eventually facilitating the entry of HIV.
And so if we are to prevent infection, we must block the entry of the virus into the host cell. One of the procedures being considered is to block CD4 receptors of infection-prone cells. However such method has not yet been suitable for therapy. Blocking the co-receptors may be more amenable. Attempts to block CCR5 and CXCR4 are under study.
In an article written by Jon Cohen (Science, 1997), A geneticist in the name of Stephen O’ Brien was featured. He discovered that an individual with a mutant copy of CCR5 gene is highly resistant to HIV infection. He also mentioned that HIV at initial contact to a cell, primarily utilizes the co-receptor CCR5 in order to get into the cytoplasm. These discoveries have raised high hopes in developing AIDS therapies and vaccines.
One aspect being considered is removing stem cells, growing them in vitro, and adding a mutant CCR5 gene. Afterwhich, these cells are to be returned to individuals. Another aspect being looked at is by producing co-receptor antagonists. These are drugs that can prevent HIV-cell membrane fusion. Examples of which are MAraviroc and Vicriviroc. However they are still under phase 2 study (AIDS: Volume 20, 2006).
Abzyme
“ In a June 2008 issue of the journal Autoimmunity Reviews,[1] researchers S Planque, Sudhir Paul, Ph.D, and Yasuhiro Nishiyama, Ph.D of the University Of Texas Medical School at Houston announced that they have engineered an abzyme that degrade the superantigenic region of the gp120 CD4 binding site (Wikipedia)”. Destroying the binding site of CD4 at the gp 120 proteins can make HIV inert. Human trials are yet to be reported.
Integrase Inhibition
Aside from reverse transcriptase and protease, the enzyme integrase plays a vital role in HIV proliferation. Integrase, also a virally encoded enzyme, is the one responsible for integrating viral DNA (produced from reverse transcription) into the host’s chromosomes, making HIV capable of replicating (Harvard University- Department of Continuing Education). Integrase can be inhibited in order to cease viral DNA integration and therefore stop HIV reproduction.
Identifying Cells that Contain Provirus
Another challenge for AIDS management is to identify cells that contain provirus. Current drugs do not do this. These calls would have no markers specific for virus, and so difficult to identify.
Antisense Oligonucleotides
A number of antisense oligonucleotides suppress specific gene expression by complementing target genetic message, leading to protein translation arrest.
Is There Any Vaccine Against AIDS?
Historically, vaccines have provided efficient means of preventing illness, disability, and death from infectious disease. However in development of vaccines against HIV, conditions maybe complicated. The task of developing a vaccine is problematic because of the high mutability of the virus.
At present no vaccines have been released that satisfy phase 3 trials. Below are some of the vaccines under study.
The first step in HIV infection of a host cell is to get into its cytosol. This is done by attachment of HIV to a cell’s CD4 receptor via its gp 120 protein coat. Once CD$-gp 120 complex is established, gp 120 undergoes conformational change that facilitates binding to one of a group of co-receptors (CCR5 and CXCR4). Trhis event establishes fusion of the virus into a host’s membrane, eventually facilitating the entry of HIV.
And so if we are to prevent infection, we must block the entry of the virus into the host cell. One of the procedures being considered is to block CD4 receptors of infection-prone cells. However such method has not yet been suitable for therapy. Blocking the co-receptors may be more amenable. Attempts to block CCR5 and CXCR4 are under study.
In an article written by Jon Cohen (Science, 1997), A geneticist in the name of Stephen O’ Brien was featured. He discovered that an individual with a mutant copy of CCR5 gene is highly resistant to HIV infection. He also mentioned that HIV at initial contact to a cell, primarily utilizes the co-receptor CCR5 in order to get into the cytoplasm. These discoveries have raised high hopes in developing AIDS therapies and vaccines.
One aspect being considered is removing stem cells, growing them in vitro, and adding a mutant CCR5 gene. Afterwhich, these cells are to be returned to individuals. Another aspect being looked at is by producing co-receptor antagonists. These are drugs that can prevent HIV-cell membrane fusion. Examples of which are MAraviroc and Vicriviroc. However they are still under phase 2 study (AIDS: Volume 20, 2006).
Abzyme
“ In a June 2008 issue of the journal Autoimmunity Reviews,[1] researchers S Planque, Sudhir Paul, Ph.D, and Yasuhiro Nishiyama, Ph.D of the University Of Texas Medical School at Houston announced that they have engineered an abzyme that degrade the superantigenic region of the gp120 CD4 binding site (Wikipedia)”. Destroying the binding site of CD4 at the gp 120 proteins can make HIV inert. Human trials are yet to be reported.
Integrase Inhibition
Aside from reverse transcriptase and protease, the enzyme integrase plays a vital role in HIV proliferation. Integrase, also a virally encoded enzyme, is the one responsible for integrating viral DNA (produced from reverse transcription) into the host’s chromosomes, making HIV capable of replicating (Harvard University- Department of Continuing Education). Integrase can be inhibited in order to cease viral DNA integration and therefore stop HIV reproduction.
Identifying Cells that Contain Provirus
Another challenge for AIDS management is to identify cells that contain provirus. Current drugs do not do this. These calls would have no markers specific for virus, and so difficult to identify.
Antisense Oligonucleotides
A number of antisense oligonucleotides suppress specific gene expression by complementing target genetic message, leading to protein translation arrest.
Is There Any Vaccine Against AIDS?
Historically, vaccines have provided efficient means of preventing illness, disability, and death from infectious disease. However in development of vaccines against HIV, conditions maybe complicated. The task of developing a vaccine is problematic because of the high mutability of the virus.
At present no vaccines have been released that satisfy phase 3 trials. Below are some of the vaccines under study.
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