the human imuno deficiency virus or HIV is a retrovirus that infects CD4 T lymphocytes among many other cells leading to the destruction of these CD4 T cells and thereby impairing cell mediated immunity and increases the risk of cancer and opportunistic infections HIV 1 is the most common species worldwide HIV 2 is restricted almost completely to West Africa
Viral Structure
the structure of the virus is that it’s uh icosahedral meaning a polyhedron with 20 Faces with a conical capsid a protein shell of a virus the capsid contains two strands of RNA the capsid also contains two enzymes essential for HIV replication the integr and the reverse transcripts the cset also contains two strands of RNA which holds the hiv’s genetic material hiv’s RNA is made up of nine genes which contain all the instructions to make new viruses three of these genes gag pole and EnV provide the instructions to make proteins that will form the new virus particles consisting of the core proteins the enzymes and the envelope glycoprotein the outer shell of the virus is called the envelope and is made up of lipid layers which are covered in spikes of the glycoproteins I mentioned here you can see glycoproteins gp41 and gp20 these glycoproteins allow the HIV to lock onto the CD4 receptors on the cd4t cells and enter the cell so let us take a look at how the virus does do this and also learn about the life cycle of the HIV um virus by looking at some key steps
Entry and Early Infection
the HIV virus gains entry into the cell you know following sexual intercourse which is a major cause once the virus is within the body they will infect immune cells which have CD4 receptors on the surface the main cells here that contain the CD4 receptors are the cd4t lymphocytes when HIV makes contact with a CD4 cell the GP 120 Spike on the surface of the HIV lock onto the CD4 receptor and another co-receptor ccr5 or cxcr4 this first step is called attachment and this step essentially will result in the fusion of the viral membrane with the cell membrane
Fusion
the second step of the life cycle is Fusion the process of fusion allows the HIV capsid to enter the CD4 cell the gp41 protein is used to fuse the HIV envelope with the cell wall the capsid releases the viral RNA the reverse transcripts and the integr as well
Reverse Transcription
the third step is reverse transcription here the HIV uses its reverse transcriptase enzyme to convert the RNA it contains into a proviral DNA inside the cell so now you have the double stranded blue DNA which is the viral DNA
Integration and Latency
once this is done the next step is integration the hiv’s integr enzyme attaches itself to the end of the proviral DNA strands and Carries the viral DNA into the cell nucleus once the proviral DNA enters the cell nucleus it binds to the host DNA and then the HIV DNA strand is inserted into the host cell DNA after the proviral DNA is integrated into the DNA of the host HIV either continues to use the body’s own cell Machinery to replicate or it will remain dormant within the cellular d DNA this stage is called latency and the cell is described as latently infected
Transcription and Translation
the next step is transcription when the cell becomes active the HIV uses the host enzyme RNA polymerase to read the HIV Gene to make messenger RNA and genomic viral RNA this is called transcription focusing on the mRNA the next step is translation the messenger RNA provides the instructions for making new viral proteins including structural proteins and the viral enzymes the viral genomic RNA and these viral proteins will prepare to be assembled
Assembly, Release, and Maturation
in assembly and release what happens is the enzymes and the HIV RNA will begin to assemble into the new viruses at the cell wall after the new virus is assembled it must leave the cell by pushing through the cell wall the virus must take lipids the fat from the cell wall to make the surface glyco proteins including the gp120 and the gp41 shortly after the virus is released from the cell the viral proteas actually cleave some of the precursor proteins which will help form the mature capsid as we know it this makes the virus mature and infectious the cycle can continue this HIV virus can then uh infect other people or infect other cells
Routes of Transmission
the root of transmission of the HIV virus is via sexual intercourse majority of cases it can also be transmitted parentally so through the blood or vertical transmission from mother to baby
Immune Response and Pathophysiology
so we looked at the life cycle of HIV and how it infects a CD4 T cell and how it also replicates within these cells but what does the body actually do when HIV infects the cd4t cell how does the body’s immune system you know respond to the HIV infection next we will focus on the pathophysiology and the na natural history and progression of HIV so what happens is you have these dendritic cells which are the first to recognize a HIV virus and present them to the immune system to mount an immune response what they do is that they engulf the virus process them and then present them on their cell surface via MHC Class 2 they then travel to the lymph nodes and what’s called the GT gastric Associated lymphoid tissue carrying this viral particle where they activate or stimulate cd4t lymphocytes the CD4 T Cell will then activate B cells and plasma cells to produce antibodies against HIV CD4 T cells will also activate cd8 t- cells also known as the cytotoxic te- cells during this time the HIV continues to infect cells the only cells that can be infected by the HIV virus are those that have the CD4 receptor these cells as mentioned are the monocytes macras dendritic cells micral cells but more specifically the the T lymphocytes the greatest concentration of these cells is in the gut Associated lymphoid tissue and lymph nodes as the virus replicates within the cd4t lymphocytes it kills the cells and spreads again
Acute Infection and Seroconversion
about three to four weeks after the initial infection the HIV viral load increases and is detected the HIV p24 antigen is also detectable the HIV antibody is detectable in weeks 2 to 4 roughly and once this occurs this is called serero conversion when you get sereral conversion where you get presence of the antibodies as well as you get this increase in the viral load this causes what’s called COC conversion sickness or COC conversion illness which manifests as symptoms of acute HIV infection interestingly these symptoms are very non-specific and they include fevers fatigue myalgia rash headache fitis and lymp lymphadenopathy really symptoms of a standard viral infection which vary and are self-limiting and go away by up to 2 weeks so in summary the acute infection which are in the first uh weeks causes an increase in viral load of the HIV virus you get the presence of HIV p24 antigen you get presence of the antibodies against HIV which actually begin to appear between weeks 2 and four and you also get the cd8 T Cell being AC activated in this period you also get C conversion illness which can be very mild and even go unnoticed
Immune Control and Viral Evasion
only a small proportion of the infected CD4 T lymphocytes allow the virus to replicate and you know get released again these infected T lymphocytes usually Express MHC class one molecules with the viral antigen which essentially tags them so that they are recognized as an infected cell which allows the cytotoxic cd8 T lymphocyst them controlling the infection unfortunately as the HIV infects more and more cd4t lymphocytes they are able to form mutations in their genetic material which allow them to evade the immune system hide from the immune system and and they do this by downregulating the MHC class one expression essentially making it unrecognizable by the immune system HIV hides within CD4 uh cells where they remain dormant
Asymptomatic Phase
HIV infection will not really cause further illness for some years and this period is known as the asymptomatic phase which is roughly about 10 years HIV in infected CD4 remains dormant and slowly reduces the CD4 uh t- cell count the viral load of the HIV remains steady because the cd8 t- cell the cot toxic t- cell keeps their numbers in circulation uh at Bay in the asymptomatic phase the viral load and HIV antibodies are detectable and remember the CD4 count will slow slowly go down here during the asymptomatic phase CD4 T cell count and viral load tests can monitor the progression of the HIV disease
Disease Progression Over Time
looking at the two stages we have learned so far using this graph with time on the x-axis we can see the viral load will increase in the first few weeks during the acute infection but then drop and remain relatively stable because the immune cells such as the cd8 cytotoxic tea cell keeps it in check for around 10 years this is the asymtomatic phase until eventually after about 10 years if left untreated the viral load will begin to increase looking at the CD4 cell count from day one of infection the CD4 cell count slowly dwindles because as we have learned the HIV infect CD4 cells such as the CD4 T cells and slowly causes them to die during the asymptomatic phase here you have serero conversion illness where the body begins producing antibodies the B cells plasma cells begin producing antibodies by weeks 2 to four of the initial infection the cd8 T cells are created to destroy the HIV infected cells HIV levels begin to fall in the blood because of this and after a few weeks to months the viral load and CD4 levels will stabilize at a level known as the set point
AIDS Definition and Risks
HIV gradually reduces the number of CD4 t- cells in the body until the CD4 cell count Falls below 200 cells uh per millimet cubed when the t- cell count is this low they are at risk of developing uh AIDS also known as acquired imuno deficiency syndrome AIDS is defined by a CD4 cell count of less than 200 cells per millim cubed or if they develop an AIDS related illness when someone has AIDS their risk of infection increases their risk of malignancy increases as well as other comorbidities AIDS defining infections are very important once the CD4 cell count drops below 200 you are likely to develop certain infections some infections develop at a much lower CD4 cell count people with a CD4 cell count below 500 also develop AIDS uh defining illnesses including carpos saroma invasive cervical cancer and tuberculosis I have a separate video that goes into lot of detail into the AIDS defining illnesses please have a look
Screening and Diagnosis
let’s talk about screening and diagnosis of HIV so what you do is if you suspect someone has HIV you can do what’s called a combination essay which is basically looking at the HIV antibody as well as the presence of the p24 antigen if positive you can do What’s called the antibody differentiation essay which essentially will tell you uh which type of HIV um the person has either HIV 1 or HIV 2 if the combination essay is negative meaning there’s no HIV antibodies present you can check the HIV viral load by looking at the HIV RNA nucleic acid amplification test or naat if the viral load is positive you can also diagnose HIV because they have viruses in the blood if the viral load is negative then this person does not have HIV at that particular time
Baseline and Additional Investigations
other investigations for HIV once confirmed firstly you know you always want to get the viral load uh but you looking at the HIV RNA and this is to look at a baseline also performing t- cell subsets to establish a CD4 cell count you can also perform vile resistant testing at Baseline for blood count eu’s lft glucose fasting lipids check for latent TB performing a tuberculin skin test and interfer on gamma release assay hepatitis viral corology corology for syphus and other sexual transmitted infections corology for toxoplasmosis as well as cervical papia
Management Overview
the man management of HIV just briefly education is very important again the infection is treatable and a person can have a normal life educate them on safe sex condoms as well as educating them on the complications of the disease and the medications treatment involves anti- retroviral therapy and it’s important to treat the person right away and it is lifelong treatment monitor for complications specifically opportunistic infections that may arise AIDS defining illnesses as well as medication side effects I will have a separate video that will focus on the pharmacology of HIV and I’ll put the link at the end of the video
Summary
so in summary HIV is a virus that essentially infects CD4 cells such as your cd4t cells and what they do here is that they replicate within the cell or they can remain dormant what they will do over time is that they will deplete the CD4 count and when the CD4 count is depleted it will increase the risk of opportunistic infections treating person with HIV early with anti- retrov therapy is important thank you for watching
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