 So, good morning, good morning, good morning everyone. So, welcome back to my channel. This is Jomar Adams once again and I'm very excited to learn with you once again. So again, I just want to welcome everyone back and I hope that you will be enjoying our opportunity and our time to learn today. So, let's dig into our topic which is very much timely and very important in our generation today. So, we are gonna talk about your human immunodeficiency virus also known as your HIV and it is very important because as medical technologists, as medical practitioners, most probably this would be one of the most common disease that we will be encountering in our practice. So, let's dig into our human immunodeficiency virus right away. So, a quick history. Let's go back to the past. Let's go back to the past and learn all about your HIV. So, the first sign of HIV pandemic actually begun in 1989 with an official report of a cluster of cases of pneumonia due to pneumocystis carainii or your pneumocystis gyrovetchi. It is in previously healthy young homosexual men in Los Angeles. So, I don't maybe already have watched a lot of documentary or a lot of movies actually with regards to the rise, with regards to the pandemic of HIV that happened in 1980s. So, most of the time, most of these patients actually appear to have a cluster of pneumonia and when they actually tested the specimens of the patient, they actually have linked it all to your pneumocystis carainii or your pneumocystis gyrovetchi. And at that time, they know that they thought that it was just simply your pneumocystis. It's just a pneumonia. But not until similar cases had been reported but on a much larger cluster of cases now, not only showing your pneumonia but also its caposi sarcoma also in young homosexuals. And that had been an alarm not only to the public but also, of course, to our health sectors. So during this time, they actually observed that most of this patient doesn't only have your pneumonia but they also are showing symptoms of caposi sarcoma. So during this time, they actually had much of the investigation and they found out that common characteristic among them was a severe and a generalized immune deficiency. So that is one thing that they actually have a hint of already. As you can see, all patients that actually are mostly young homosexual men, they actually observed that not only does they have pneumonia but they also have caposi sarcoma and eventually they found out that all of these patients are also immuno-suppressed or are immuno-deficient. So as you can see, that is the appearance of a caposi sarcoma. So not until Francois Barré-Sinosi and Luce Montagnier isolated a sample from a patient in 1983 that was also taken from a male homosexual that they actually was not unprecedented. They actually would found out the causative agent or the underlying cause of these diseases. Of course, we know that caposi sarcoma is caused by your herpes, your pneumonia is already caused by your pneumocystis carini, but they actually know at the time, they actually are hypothesizing that this must be something bigger than those virus and bacteria causing it. So at the time with the identification of the virus, agents were soon developed. So it was these two great scientists who discovered your human immuno-deficiency virus and during that time, they know that they have to work fast similarly to what is happening right now in our case now that we have your ECQ because of the pandemic corona virus. So during that time, after the identification of the virus, reagents were immediately developed. So they have to develop reagents that would identify, that would actually help in the diagnostic processes and eventually with the reagent, it was proven that earliest case of infection by HIV-1 came from a person in Central Africa in 1959 and imagine that it was around 1980s when they found it out and most of the patients that are actually showing pneumonia and even your Kaposi sarcoma are already patient with advanced stage of not just HIV, but of AIDS. So during that time, they also was able to identify in the case of the 1986, the 1980s pandemic, they were actually able to identify that it was your human immunodeficiency virus 2 that was identified in those patients. So roughly we actually have two strains. We have your HIV-1 and we also have your HIV-2. One that was actually found out in Central Africa and the second one, your HIV-2 was the one that caused pandemic in the States during the 1980s. So HIV now is recognized as a zoonotic disease that entered the human population from chimpanzee. So this might have been another spillover to from animals now going to humans. So it was believed that this HIV, the virus actually came from a population of chimpanzee and these virus are somehow related to the group of more than 40 simian immunodeficiency virus or your SIV. So similar to what they actually found out in your chimpanzee, they actually saw that most of those cases are actually similar to your SIV. So that is what do they believe the ancestor of your HIV. So meanwhile, after that, there are four distinct client lineage of your HIV-1 sequence that has been identified. So there are different, your HIV have two serotypes, you have your HIV-1 and you have your HIV-2 and HIV-1 can actually be further classified into M, N, O, and P. So the group M is a predominant lineage of HIV worldwide and detailed study on the sequence of HIV showed that groups M and N were actually derived from the simian immunodeficiency virus that was found in chimpanzee. So during this time, most probably that maybe you are wondering how it was transferred since it is somehow actually transmitted in some sort of other transmission like vertical transmission which obviously cannot happen to chimpanzee passing it to human but if you're gonna look at it deeper, it actually has to do something about bestiality practices during that time as well. So afterwards, we also have your groups O and P that were derived also from an SIV found in the Western Lowland Gorilla. So if the M and O, M and N are actually found on your SIV on the chimpanzee, your O and P are actually from your gorilla. So HIV-2 is derived also from your SIV. So aside from that, your HIV-2 and HIV-1 are somehow all related to those animals. So the transfer of HIV-1 group M lineage occurred in or near Kinshana in the Democratic Republic of Congo around 1920. So it was believed that even around 1920s, the HIV was already passed on to humans from the animals. So it in Kinshana, Congo, Republic of Congo. So HIV, for the information of everybody, HIV is actually a member of the genus called Lenti Virus or the Lenti Verde Day. And both of them, HIV-1 and 2 are both member of the genus. So they are from the family of retroverde day. So when we say retroverde day, they are actually, they do have RNA, their main genetic material is your RNA. That's why your retrovirus can insert its RNA genome to the whole cell via reverse transcription. And eventually as we go along, I'll be mentioning three major enzymes used by our HIV for it to be able to thrive within the host cell. And more specifically, what type of cells do they infect? Because they are very much specific about that. So common features of Lenti Virus infection includes infection of the bone marrow derived cells, integration of the DNA copy of the viral genome into the host DNA. And again, if we're gonna go back to our discussion about coronavirus before, as you can see, most of our, almost all of our viruses cannot produce its own genetic material. They cannot produce their own genetic material. That's why they have to hijack the cell, the host cells, DNA machinery for it to work on their favor. So, they are also characterized by persistent veremia and of course of lifelong infections, prolonged subclinical infections, weak neutralizing antibody responses again, due to immunodepression, immunosuppression, rather, and continuous virus mutation and antigenic shift. All right. And aside from that, it is also included neuropathology on your Lenti viruses. So, this is actually your HIV. As you can see, your HIV is an example of an envelope virus. It has an envelope, it has an envelope and as you can see, it has a cup seed, a nucleo cup seed. The nucleo cup seed containing now your very important viral RNA genome for it to be, to replicate. And as that, during at this time, I just want to mention three major enzymes that your HIV uses for it to be able to hijack your host cells DNA machinery. We have here your protease, we have here your integrase and of course, the infamous reverse transcriptase. So as you can see, these three enzymes are very important. But aside from that, maybe you're wondering how does the HIV knows what particular cell does it will it infect? And to be honest, it's actually so genius that it actually is targeting one of the major immunoregulatory cell within our body and that is your CD4 positive cell also known as your T helper cell. So how does it knows that? How does it identify the CD4? First, it has actually two glycoproteins. So we have your glycoprotein 41, which is a transmembrane protein. As you can see, it protrudes from the envelope outward where you can see your glycoprotein 120, which is a docking glycoprotein. And in general, together that is glycoprotein 120 and glycoprotein 41 is glycoprotein 160. All right. So so much about that. Let's move on. So the structural proteins of your HIV are glycoprotein 120, which is the one that binds to the CD4 receptor. So it's similar to a lock-and-key method. So a particular key is only specific for a particular lock. And that is how genius the HIV was that its key is only specific to the receptor found on your CD4 cells. Aside from that, you also have your glycoprotein 41, which is a transmembrane protein that mediates the virus-membrane fusion with the host cell. So these two glycoproteins are very important because upon the binding of glycoprotein 120 and the CD4 receptor, the envelope of the virus needs to fuse now with the envelope of the host cell, eventually entering the host cell. So that is the job now of your GP 41. And when it comes to the HIV replication, so now we know that it is GP120 that attaches to the CD4 receptor. It is your GP it is your GP41. Okay. It is your GP41 that mediates the fusion of your viral membrane and your host membrane. Now we go to the HIV replication, the seven stages of your HIV life cycle. So the first one is binding and this is the job now of your glycoprotein 120. After binding of your glycoprotein 120 to the CD4 receptor, it will now start the fusion and this is not the job of your glycoprotein 41, a transmembrane protein that initiates the fusion of the viral membrane and the host membrane. After that, it will now be liberating the genetic material alongside with the three major enzymes that I mentioned a while back, your reverse transcriptase, your protease and your integrase. What happens next is that the RNA is now liberated within the cell and it first need to form its complementary DNA with the help, of course, of your reverse transcriptase. So reverse transcription happens whereby the RNA makes a copy of your single strand complementary DNA. And as you can see, if you're going to look back in the central dogma, that's not how it happened within the body. First one you have your DNA and then it will be undergoing transcription for it to become your RNA. But for the case of our viruses, it's not the same. They have the RNA and they will reverse transcription it into becoming a complementary DNA. And afterwards, what happens? So in the reverse transcription, it is the reverse transcriptase that does the work, that takes care of everything. When it comes to integration, I wonder if you can guess what enzyme it is. Okay? Yes, correct. It's your integrase. In the integration, what happens now is that isn't it after the reverse transcription? You already have now the viral DNA after reverse transcription. And that viral DNA needs to be integrated within the host DNA and that will now be the job of your integrase. It will integrate the viral DNA into the host DNA so that when transcription happens and when translation happens, it's not just the host cell or the host protein that will be produced but also your viral proteins and viral genetic material. After that, there will be replication. The viral DNA now will start to be replicated to be duplicated and afterwards, after transcription and after translation, okay, we have now your proteins and also your RNA that was produced after your processes. And that is the time now where the HIV is ready to assemble. Yes, it's similar to your Avengers. They also would assemble. And that is now the job of your protease. It will now start to trim some proteins that are needed and are not needed. And afterwards, after the assembly, they will now start to bud off using the cell membrane of your host cell and then they will now be free on your bloodstream and then go and infect another CD4 cell or worse, go and infect another person. And that's what's happening. And let's go to each in every step. I actually have given you the route up already. But in the binding, it's also known as your attachment. So the HIV binds to your receptor on the surface of your CD4 cell and that is your CD4 receptor. Again, this is the job of your glycoprotein 120. And at the same time, right after that, there will be a fusion of your HIV and your CD4 cell membrane with the help now of your glycoprotein. What correct your glycoprotein 41. So afterward, reverse transcription happens. HIV releases your reverse transcriptase converting now your HIV RNA to its complementary HIV DNA. This allows now the HIV to enter the CD4 cell nucleus and combines with the cell genetic material. So as you can see, your nucleus it has your nuclear pore where your materials or the viral genetic material could enter. And what happens next? It's your integration. Correct. The integration is done by your integrase whereby it integrates the viral DNA to the host DNA eventually following the replication whereby the HIV uses the machinery of your CD4 cell to make long change of HIV protein. And afterwards when protein is fixed, protein is all present. We can now start to assemble. So the HIV protein and HIV RNA move to the surface of the cell and assemble into an immature HIV. We say it's immature because it doesn't have its own it doesn't have its own membrane yet. But right after budding, the immature HIV pushes itself outside the CD4 cell and voila! It's now liberated. So the process of budding the release of protease breaks the long protein chain to form the immature virus. Then smaller protein will combine to form now your mature HIV. And this is how it looks like. Okay. This I hope you can see my cursor because I will start to do some pointing. So this is your your HIV. As you can see as the job is in your your CD4 receptor and your CCR5 or your CCR4 coreceptor both bind to your GP120 at the fusion will be initiated by your GP41 all throughout to the reverse transcription to the integration to the transcription to the assembly and eventually to the budding off of your HIV. So that is how it happens. I hope it is very clear so I want you to follow through the arrows here. Malay nyo this would be the question in your homework. So please do familiarize yourself when it comes to when it comes to the HIV replication or the life cycle of your HIV. Okay. Moving on now. Okay. Moving on. We also have here your HIV replication. So this is just the reiteration of what I mentioned a while back from budding from fusion from reverse transcription to the integration to the assembly and eventually to the budding off of your HIV V. All right. So there are actually stages of HIV infection. The first one is the acute HIV infection the clinical latency and eventually when it progressed now to your acquired immunodeficiency syndrome. So I want you to be familiar with what is HIV? What is AIDS? What is COVID-19? Because that is very important. All right. So for the stages of HIV we have your acute HIV infection and it is characterized within two to four weeks after infection people may actually experience a flu-like illness that may last four weeks. So to be honest to be honest I've talked around I actually have talked around talk to other people and most of them actually have experienced this really after after a contact with a particular person they would start to develop flu-like symptoms which actually is very much negligible at that time because they would actually thought that it was just a common flu and nothing serious about it but apparently that's the early stages or the acute stages of your HIV infection. Afterwards comes now your clinical latency or also known as the asymptomatic HIV or chronic infection. This happens when HIV is still active but produces at a very low level. Okay? At the end of this stage the viral load goes up and the the CD4 count goes down. Obviously the CD4 goes down because this is the main cell that is being targeted by your by your virus. So here you can actually won't see any infectious or any symptoms at yet but the moment that the HIV is now active the HIV now the viral load goes up the CD4 count now would start to drop and leaving the patient immunocompromise. And afterwards when the patient is already immunocompromised it will now be progressed and will be diagnosed as acquired immunodeficiency syndrome. And this is the more severe stage of HIV infection because of a bad the damage immune system. It increases the number of opportunistic illnesses and eventually your caposis or coma your oral thrush and even tuberculosis. And maybe you're wondering Sir, why does the HIV causes now your immunosuppression? So let's go back to the role of your CD4 cells. And this is not part of the PowerPoint so I just want you to take down notes and listen to this. So your CD4 positive cells also known as your T-helper cells is actually the main signalling cell within your immune system. So whenever there is an opportunistic pathogen that comes inside your body it is the job of your T-helper cell to signal to call all immunological cells and eventually even release some cytokines some interleukines that will be needed for the production of antibodies and for the production of an immune response to the virus. And if it happens that the one that actually signals the entire system is missing it went missing it was already depleted there will be no signalling cell within your body saying that hey we have an infection we have to be heightened and that's the time now where opportunistic illnesses comes inside your body unknowingly and leaving now your immune system vulnerable and compromised that's what happened okay so how does your HIV is being transmitted from one person to another so we already know that it originated from chimpanzees from gorilla and eventually it was actually past among humans already and usually one of the main cause is unprotected unprotected sexual intercourse sharing of needles so some of the intravenous drugs that was very infamous during that time we also have blood transfusion reason why during blood transfusion we actually have major blood-borne diseases that are being detected one of those are your HIV you also have your hepatitis B your syphilis or your ya your syphilis or your treponema and then we also have your malaria some also are including CV and in some cases they are also including CMV as well organ transplant is also one mother to baby during pregnancy because the virus can cross the placenta and eventually not only can it cross the placenta you know that there's a maternal fetal fetal connection when it comes to the blood supply so the CD4 can even go to the baby that is and number five you also call it vertical transmission so talking about now about a different transmission as you can see the increase of HIV cases not only here in our country but worldwide starting to really be so alarming so the HIV cases here in the Philippines actually starts to increase and increase and increase each year as you can see from 2017 to 2018 to 2019 the records continue to increase one of the main reason probably is that more people are getting tested compared before that's one so awareness is actually being awareness is already a friend to us but then okay the more alarming case is that more of these cases are actually teenagers as young as 15 and even younger than 15 which is somehow very alarming to be honest and when it comes to the HIV cases as you can see more most of the transmission so I am giving you a graph of the distribution of how HIV is transmitted so only one percent are actually due to blood transfusion thank God because we have an effective blood bank system here in the Philippines three percent are from needle sharing because IV drugs is not that very famous here in our country so they actually use to sniff rather than inject themselves with drugs aside from that we also have drug to mother to child we also have here now our sexual intercourse and as you can see much of the percentage actually came from your sexual intercourse and if we're going to break down that 11% of that is actually from heterosexual sex so male female sex 21% actually are sex with both male and female among males so this is very alarming as well but the chunk of the graph actually lies with male to male sex only so for the homosexual even in the 1980s it started to increase in the homosexual man community around 58% that now leads us in a proportion of report death among people with HIV by transmission is that more people actually as you can see comparing our data from the January 1984 to September 2019 as you can see there has been an increasing cases of death among deaths among HIV patients because of the transmission due to male to male sex so 63% imagine that that's really big so it's very important we are talking about so one of the reason why I I am mentioning that the increase in the cases are because of increasing awareness and increasing testing capacity of our country so testing for HIV should be voluntary which is another story for another time if you wanna check on that I can we have a video on that that is RA8504 we have three parts video regarding your HIV and regarding the law that concerns our fellow men with HIV aside from that the testing is also two phases okay we actually have two phases of HIV testing that is actually one for the screening and one for the confirmatory testing so aside from that okay aside from that we also have HIV counseling both pre-counselling and post-counselling we also have to have an HIV testing facility with HIV profession and of course I just wanna emphasize something so HIV counseling is different from HIV testing so medical technologists are mostly the one that are HIV proficient the one that can perform the test and for HIV counseling these are from nurses from psychometration to physician and even medical technologists as well so they do the counseling pre and post testing so I think we're coming to an end so laboratory diagnosis are usually the identification of your HIV-1 to either antibody or antigen using an immuno assay so the confirmatory test is your western blood maybe you have you came across with RIVDA maybe you came across with RIVDA but RIVDA is just an algorithm a rapid HIV diagnostic algorithm so again if you wanna go into that deeper you can actually visit another video that is your RA-8504 please do watch it so that you would have a deeper understanding of this lesson aside from that you also have your nucleic acid test or your nucleic acid amplification test that actually removes or actually there is no need for a window period phase anymore so most of the time most of the time this actually have contributed to the low level of HIV transmission in blood samples because they actually use NAT test to check HIV in blood blood bag units okay so this is actually the rapid on your left that is actually a screening screening test as you can see we have here a control line in the test line so if there is two line that is positive similar to your pregnancy kit but if you have one line but be sure that the one line is the one line that remains is your control line that is negative or non reactive without HIV if one line is present but it is off the test the test line and none of the control line that is invalid and if none of the none of the line appeared that is considered what that is considered invalid so moving to your right that is actually your Western blood Western blood is actually your confirmatory test and for us to be able to consider it a reactive or a positive result there should be at least two bands coming from your either GP120 GP160 your GP41 or your P or your core protein 24 so remember that okay remember that so if you have a band that is actually 120 41 that is already positive at least two of those three okay either of that either of those combination but at least two bands okay but right now we don't have any treatment or vaccines against your your your virus that can effectively kill it but what we have is actually an antiretroviral drug it actually targets some of the key function or the key key mechanisms on how the patient is being infected we have your CCR5 which is a receptor of your CD4 we have also post attachment inhibitors we have fusion inhibitors inhibiting your GP41 we also have your non-nucleoside reverse transcriptase inhibitor aside from that you also have another reverse transcriptase inhibitor we have your integrase inhibitor and protease inhibitor in a nutshell what I'm trying to say is that most of the drugs are actually targeting either your cell your cell receptor your glycoprotein or the enzymes that are key in the transmission of the disease are we clear? okay so so much about that thank you so much for keeping up with me so if you have any questions clarifications comments so please comment down below on my YouTube channel and if you have some things that you want to ask privately you can email me you can send me an email at jagandingattoa.edu.ph so that would be all for today this is Jomar Adams once again so please do like share and subscribe this video and please do subscribe so that you will be updated for the latest posting in my channel so I'll leave you with this saying Strive so tomorrow you can try thank you so much and have a great day good night good day good afternoon whatever have a great day see you soon