How HIV infects us: CD4 (T-helper) lymphocyte infection | NCLEX-RN | Khan Academy

How HIV infects us: CD4 (T-helper) lymphocyte infection | NCLEX-RN | Khan Academy


– So now we’re in the lymph node. We’re looking at how HIV,
brought to the lymph node by either one of our
well-intentioned dendritic cells or maybe by a macrophage,
manages to infect our T helper cells, a.k.a.
our CD4 lymphocytes. Well, it all sorta
comes down to receptors. On our T helper cell membranes, we have two to three
receptors that help HIV gain access to these cells. We have the CD4 receptor, which is sorta the primary receptor that HIV needs, and we have either one or
both of CCR5 and CXCR4, CXCR4 being much less prevalent. CCR5 is really the preferred co-receptor that most strains of HIV need to bind. But these are both called
co-receptors in this context here. So, what’s important about
these particular receptors is that HIV happens to have a protein, This thing here called
Gp120, on its envelope. The outer part of the virus here, that interacts really
well with these receptors. You can almost think of it
as a lock and key setup. These receptors here are some of the locks that need to be open to gain
access to our T helper cell, and unfortunately for us, HIV has the key. This Gp120 protein on its surface. So how does it work? Well, Gp120 on the HIV envelope, it first binds the CD4
receptor on a T helper cell. This binding between
the two sort of induces a confirmational change in
the CD4 receptor protein here, and it allows our co-receptor
here, either CCR5 or CXCR4, to grab a hold of this complex
and pull the viral membrane and the T cell membrane closer together. And when they get close enough, this little stalk here, the
stalk of the Gp120 protein, it sorta pierces through
our T cell membrane, and it pulls the viral
and the T cell membranes even closer together, and
what ultimately happens is that the two membranes
will fuse together, which allows the HIV particle
to essentially inject, now that it has access to the
inside of our T cell here, it injects its genetic
material into our T cell, inside this viral capsid here. And that’s in the form of
viral RNA, ribonucleic acid. And this envelope is just sorta left at the surface of our T cell here. So once this capsid with viral RNA and some viral enzymes enters our cell, it gets degraded by some
of our cellular enzymes. And this is essentially another
bad move on our cell’s part, because it releases the viral enzymes and the viral RNA which
can now get to work on taking over our T cell. We kinda just got Trojan-horsed in a way. And, you know, most viruses at this point are happy to just use
our cellular machinery like our ribosomes and our
cytoplasmic nucleotides to make copies of themselves,
and they leave our DNA alone. But not HIV, HIV’s a little
sneakier than normal viruses. And probably the key viral
enzyme among all of these that allows it to be so sneaky is this reverse transcriptase enzyme. So what reverse transcriptase does is it takes this viral RNA
here, the one that came with, and it uses some of our nucleotides that are floating around in the cytoplasm, to revert this viral RNA
into a single strand of DNA. It uses the viral RNA as a template to synthesize a strand of DNA. And then it synthesizes a
complementary strand of DNA for the single strand,
so we end up with some double-stranded viral DNA here. And so right now, alarm bells are probably rightfully ringing in our head, right, we just went from single-stranded RNA to single-stranded DNA
to double-stranded DNA, that’s not supposed to happen. Remember the central dogma
from your biology classes that said “we go from
DNA to RNA to proteins,” and here we are doing the
exact opposite of that? Well that’s exactly what’s happening, we are doing the opposite, and that’s why HIV is called a retrovirus. It subverts the central dogma and it generates viral DNA from viral RNA. Outrageous! The other sneaky thing
about reverse transcriptase I wanted to mention is that
it makes a lot of errors doing all this polymerization,
all this synthesis. It doesn’t quite have
the proofreading ability that our DNA polymerase enzymes have. That obviously come in handy
when we’re replicating our DNA. So on a practical level,
what this means is that, well A, lots of viral
polymerase errors equals lots of mutations in the viral DNA. And that means that over
time, the virus can develop resistance to certain
antiviral medications, because the medication eventually might not be able to even
recognize the viral DNA. And B, it’s really hard to
make a vaccine against HIV because even small changes
in the genes of the virus might render the vaccine ineffective. Remember, we’re talking
about one cell here, and the mutations that
happen within one cell, but keep in mind that there’s potentially gonna be millions of HIV-infected T cells in which HIV will be
mutating ever so often. And actually, this reverse
transcriptase enzyme is one of the targets for some of the medication we use
to control HIV levels. We try to block this viral reverse transcriptase enzyme from working. Anyways, back to our now
double-stranded DNA here. Another viral enzyme called integrase will come along and grab hold of it. It’ll then bring it to
the T cell’s nucleus and carry it through
one of our nuclear pores into the nucleus.>From there, and this is sort
of the point of no return in an HIV infection, the
integrase enzyme nicks, it makes a little cut
in our human T cell DNA, and it allows this double-stranded HIV DNA to integrate itself into our DNA. And this step essentially establishes the lifelong infection with HIV. The viral DNA has sort of, now become congruent with our own DNA. So from here, a few
different paths can be taken. Well, either this DNA
just sits here and just, and isn’t actively transcribed into mRNA, and we call this a latent HIV infection, when your cell has integrated
viral DNA into your own, but is not actively doing
anything with that DNA, or your DNA transcription
enzymes might come along, this is usually the more
likely thing that happens. So let’s say RNA polymerases come along. Well, it’s gonna transcribe
this viral DNA here just as if it was your own DNA, so it’ll start cranking
out viral mRNA transcripts, which then leave the nucleus,
they find some ribosomes, they, on the rough endoplasmic reticulum, and they start to use the
ribosomes to make proteins like new envelope proteins for example. These envelope proteins
will then make their way through our endoplasmic reticulum, head up toward the cell surface, right, our cell membrane,
and once enough get up there, they start to coalesce a
bit, they cluster together. And this is actually happening in a lot of other places
on our cell membrane. See, you can see all
the new Gp120 proteins here on the surface of these
viral envelope segments. And while this happening,
another key viral protein is being made at the same time. Actually, it’s a viral polyprotein, “poly” because it’s
essentially multiple different viral proteins laid out end-to-end on one long protein strand. So, these will include those viral enzymes we talked about earlier, right, reverse transcriptase, integrase, as well as some other proteins that the virus needs to be infectious. So, all of these long viral polyproteins, along with some viral RNA,
they also get brought up to the surface, to the areas where all the envelope proteins
have clustered together. And so now, all of these components can come together to start forming a new, immature HIV particle. And I say “immature” because it’s not quite ready to infect other cells yet, one more thing has to
happen before it matures and it’s ready to be infectious. It needs help from yet
another viral enzyme, called a protease. Proteases are special enzymes
that cleave up polyproteins just like this one here,
into smaller proteins. But they only cut at
specifically marked sites. And this protease here, it does just that with this long viral polyprotein that’s been made using our ribosomes, so it snips it at a few different sites, and we end up with what
all are the components that an HIV particle needs to infect, so for example, this might be its reverse transcriptase here, and this might be
integrase here, and so on. So the protease starts cutting things up, and while it’s doing
its slicing and dicing, these components here,
together they all start to bud off the T cell as a new virion. And shortly after it buds off, the protease is finished
cleaving this long protein up. So this is now a fully
mature HIV particle, now that it’s used this T cell to be made, it’s ready to go on
and infect other cells, particularly of course, T helper cells. But what happens with this T helper cell that was infected? Well, our old understanding
of it was just that as tons and tons and tons of new virions budded off of our infected T cell, all of that budding off would
actually kill our T cell. But recently it’s been discovered that things are a lot more
complicated than that. In the vast majority of cases,
the T helper cell does die, but it’s not because of the
budding off of the virions. It’s most often because infection and subsequent production
of HIV particles, it sorta triggers this sort of self-destruct mechanism within the T cell. But I’ll cover that in more detail when we talk about how
HIV kills our T cells.

43 Replies to “How HIV infects us: CD4 (T-helper) lymphocyte infection | NCLEX-RN | Khan Academy”

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  2. I have a 4 generation HIV done at 28 days and 41 day its come back negative can it be fasle negative and can be really positive?

  3. I wonder if there is another virus out there that is so PREFECT of a criminal 🤔 It makes me suspicious about the evolution of it😩 It is “A PERFECT BORN VIRUS” 🦠🧬🔬🧪

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  5. This is exactly what I was looking for. I have been seeing tons of videos about how HIV infects CD4+ cells, but non of them go to the details of the cell signaling process I want to know. Thank you!

  6. Is it true that in tge accute hiv phase (first 3 mth) the cd4 cells number shoult count down verry fast?! A higher limit of cd4 cells arter some mounths, could eliminate the risc of infection?!

  7. It's widely accepted that HIV enters the cell via clathrin-mediated endocytosis. It does not fuse with plasma membrane

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  9. Why cant we Apheresis the blood then treat after a stem cell harvest on electroporation gel the stem cells with crispr cas9 guided by knockout rnas for ccr5 cxcr4 tat and rev. And then reintroduce the cells into the human?

  10. Waiting for microscopic video ….
    Otherwise all illness symptoms are similar to inhalled or digested radio active particles …..

  11. that was very elaborate how come there aren't millions of views you are amazing I must say

  12. Been using this as a reference since the first time we tackled HIV in my undergrad years and up until now in my 2nd year in med school!! 💖 this will always be one or my favorite and mastered lessons!

  13. really great video and really liked it but now i need to say something in my language. olum boyle bir orospu cocuklugu yok. lan bu nasil bir sey arkadas ya.

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