Pathophysiology

So!  How does this thing - HIV - work?  Well, this is what it looks like! =)

Unfortunately folks, there is no real easy way to explain HIV so forgive me while I get a little technical for a bit here!

HIV is not the common type of virus most people have heard of, but rather, a lentivirus or a “slow” virus.  Like viruses, which must use the mechanisms of a cell to reproduce, HIV can’t act of its own accord – it too must have a host.  What distinguishes these retroviruses from other viruses is their mode of replication.  They use a combination of RNA and what is called a reverse transcriptase.  This genetic material is encased in a series of proteins that not only protect it, but allow it to dock and gain entry into its victims.

Two strands of RNA lie within what is called a capsid which is made up of about two thousand viral proteins called p24 and protects the delicate material until it is within the host cell and able to insert itself.  Next to these strands are the reverse transcriptases which will eventually allow the creation of a strand of DNA.  Two other proteins make up the interior of the virus: p7, which makes up the nucleocapsid and envelopes the strands of RNA; and p17, which makes up the matrix and borders the lipid membrane.  This viral core, as mentioned, houses this genetic strand, which is made up of nine genes.  Three of the genes – called gag, pol, and env – serve as the creators of the parts which will eventually make up new viruses.  The remaining six perform regulatory actions and are called tat, rev, nef, vif, vpr, and vpu.  These tend to deal with how the virus interacts with other cells and how the virus goes about replicating itself.

Surrounding the outer membrane of the virus is a series of proteins derived from a special protein made by the env gene called gp160.  This protein is broken into binding molecules of glycoproteins called gp120 and gp41.  These are what allow the virus to bind to receptors on the cd4 T-helper cells and eventually fuse with and penetrate the membrane.

So, in essence, what happens when the virus is introduced into the human body is that it is virtually served to its victim on a silver platter.  The most commonly known route of entry for HIV is transfer by sexual interactions whereby the virus enters the system through mucous membranes where it is picked up by macrophages and dendritic cells.  These escorts then proceed to the lymph nodes where they present their invaders to the cd4 T-helper cells allowing for the initial establishment of infection.

Once they have breached the system, they begin their hostile takeover.  The glycoprotein 120 receptors on the surface of the virus bind to specific receptors on the surface of the cd4 cells where they then begin the process of fusing with the cell’s membrane.  This is accomplished with the aid of the glycoprotein 41 unit which pierces the cells membrane allowing the two membranes to become one and introducing the capsid into the cell cytoplasm.  In the process the remaining gp120/gp41 complexes spread out across the surface of the new host cell.

This is where the reverse transcriptase comes into play.  Once inside, the capsid surrounding the viral RNA is dissolved and the p31 transcriptase is used to create an actual piece of DNA with all the complimentary encoding.  This string of DNA then forms a circle and enters the nucleus where it is inserted into the cell’s DNA, with the help of a protein enzyme called integrase, and is now termed a Provirus.  At this point, the virus can lie in wait for several years or it can proceed to duplicate itself with the help of its host.

There are two methods by which this new virus driven cell can take over other cells in its vicinity: budding and syncitium.   Budding can be quite devastating to the host cell.  To bud, the virus must replicate a new set of proteins to form new copies of its self.  This is accomplished with the help of its host using an RNA polymerase to create a messenger RNA, which is then moved out into the cytoplasm where it can be translated by a host ribosome into a variety of proteins.  This is one of the areas of production that cause HIV to be so tricky for researchers to get the best of this virus.  It seems that HIV tends to make a lot of slight errors when it replicates, pumping out hundreds of thousands of different variations of its self.  In other words, even if there isn’t a mix up in the translation there can certainly be a blending when they are put back together.

These proteins are reassembled to form the viral RNA and the capsid.  The outer membrane encompasses the new capsule, which then fuses with the outer membrane of the cell.  The receptor complexes merge with the rest of the membrane of the host and the new viral cell is ready to bud off and find a new host cell to take over.

The other method, by which the virus can usurp a neighboring cell, is by a process called syncitium.  In this case the infected cell literally absorbs what it comes in contact with.  When the viral host cell comes in contact with the new cell, their membranes fuse becoming one big cell.  All in all, this invader will overwhelm and virtually consume the entire immune system.

The pictures up above here are from the virtual patient reference library at the Carl J. Shapiro Institute of Education and Research at Harvard Medical School and Beth Israel Deaconess Medical Center.  The information gathered here came from my days in the BSN program; specifically from Pathophysiology: The biologic basis for disease in adults and children, 5th ed. by McCance and Huether.  Also from a particularly enlightening lecture in my Care in Illness class from a graduate student and now an HIV ARNP clinician name Karen Dykes.