Midterm Preparation Lecture 2 HIV.docx

Lecture 2 HIV General global distribution of HIV infections. Epidemics not confined to one specific place in the world so it becomes a Pandemic = HIV virus is an example of a pandemic General temporal trends in HIV infection rates. Not proportionate around the world though The impact of this disease isn’t felt equally or uniformly around the world Prevalence  Adults with HIV + , mostly the sub-saharan Africa, (south Africa etc) and Russia 43 years old on average to live before they die 60% of the infected hiv people are living in sub-saharan Africa 90% + of <15 year old children living with HIV are located in Sub-saharan Africa People with HIV is gradually increasing over time Factors that explain why no cure or universal vaccine has been developed for HIV/AIDS.  Constantly changing continues to evolve over time so even if we do find some kind of cure right now it may not work anymore over time.  Conspiracy theories, maybe it’s because if a cure is developed, many people with the infection will want to take the cure instead of consistent treatment so the companies that offer the HIV treatment would lose money because of the developed cure that would only be needed to be taken once in a person’s lifetime.  Our immune system doesn’t carry any defenses for HIV  There are multiple different strains of HIV because it keeps on changing so a drug or a vaccine that defends one of these strains may not work for the other types. Reasons why viruses are not considered “alive”.  Where would viruses fit in the tree of life?  NO WHERE… but why?  Because viruses are not ALIVE!  They cannot self-reproduce, they can reproduce but in order to do so they need a host (parasites), they don’t have their own metabolic processes because they are not formed by cells.  Being cell-based/cellular is a necessity to be considered as alive.  Viruses are not cells, they’re much smaller than cells Reasons why anti-viral drug therapies often have serious side effects.  In order for a virus to reproduce, they have to get into a cell/host cell to reproduce.  They use the host’s cells metabolism to reproduce  So if an anti-viral drug is taken, we can’t inhibit the virus without also killing the host cells.  This is because the virus is using the host cells machinery/metabolic processes, and so by taking the anti-viral drugs to kill the virus, damage will occur to the host cells that are infected with the virus which will result in some serious side effects.  Doctors don’t recommend or prescribe these anti-viral drugs very often, because they cause serious side effects (collateral damage) Major steps in life cycle of HIV.  Retroviruses  unlike every cell-based life, retroviruses like HIV do not store their genetic information in the form of DNA, instead it’s stored as RNA.  So, in order to intergrate themselves into the hot cell, it has to go through a step called reverse transcription.  Using RNA as a template to synthesize DNA.  No proofreading processes associated with reverse transcription  Reverse transcription has a huge rate of errors, like for example adding a wrong base to the chain  results into mutation, mutation rate in HIV is a million times higher than mutation rate in humans.  There’s a high mutation rate due to reverse transcriptase  What’s reverse transcriptase? Usually the life cycle of a living cell is synthesized from the genetic information in the form of DNA. It is transcribed to RNA which is than translated to protein with the help of ribosomes on the endoplasmic reticulum. As you can see, this life cycle is uniform, meaning the process cannot go backwards from protein to synthesize DNA. But the process called “Reverse Transcriptase” is an extra step to the life cycle. It is used for viruses for example to reproduce, by reverse transcribing their genetic information which is in the form of RNA to DNA in order to undergo a regular life cycle. DNARNAProtein. This is the main reason why viruses are not considered as being living organisms because they can’t self-reproduce. They need a host cell’s metabolic processes in order to undergo reverse transcriptase and then reproduce.  Difference between Retrovirus and a normal virus o Retrovirus has to go through reverse transcription in order to obtain DNA and reproduce o Normal virus, most of them, already have their genetic information in the form of DNA so they can transcribe them to RNA and then translate them to proteins. Specific role of integrase and reverse transcriptase in retroviral life cycle.  Retroviral life cycle:  Virion = HIV particle, enters the host cell and injects its genome (RNA) and the few proteins that it has into the host cell.  One of the viral enzymes “reverse transcriptase” reverse transcribes the viral RNA into viral DNA.  Why the viral RNA has to become viral DNA? … Because it needs to be DNA in order to enter the host’s chromosomes.  Another one of the retrovirus enzymes is “Intergrase” which is a splicing enzyme, inside the nucleus of the host the viral DNA gets inserted into the host’s genome/chromosome  At that point, the hosts cell physiology is hijacked, the viral DNA is transcribed to viral RNA and then translated into viral protein which are new virions assemble at the surface of the host cell, they bud off or lyse (exit the host cell by killing it) to infect other host cells.  Takes down the hosts immune system by replicating itself, and if the virus doesn’t kill the host cell as it exits, the infected host immune cells will be recognized by other immune cells and taken down that way.