There are many viruses that you can have yourself vaccinated
against, and sometime, like in the case of small pox, the vaccination can
completely eradicate the virus from the face of the planet. HIV, however, is not
one of them. It changes frequently and has evolved into many different strains
presenting with varying behaviour. These strains can be so different that some antiviral
drugs can be efficient only against one of them but not another.
One of the ways these strains differ is how they enter cells.
You can think of a cell as a large room with many doors leading to it. And of
HIV virus as a small malicious robot that enters these rooms and consumes them
from the inside to manufacture its own copies. To open the doors, the robots
have specialised arms. However some strains of the virus have arms that can
only pull handles, while others can only turn knobs. This is mirrored in
anti-HIV medications. For example, following this analogy, some drugs act as
attachments that you put on the knobs to give them rectangular shape. The
knob-turning virus won’t be able to grab it and get inside the cell anymore.
However, the same drug won’t affect the handles and therefore have no effect on
the handle-pulling virus. There are also strains of HIV that can both pull
handles and turn knobs, but that’s a different story.
A recent publication (1) has revealed that our platelets (the tiny
cell-like structures in our blood responsible for clotting) can secrete quite large
amounts a long known protein called platelet factor 4 (PF4) that actually gets
in the way of HIV infection. It does so by a mechanism similar to the one of
the drug turning a round knob into a rectangle, but this protein does not bind
to the doors on the cells, but instead to the virus arms. The data suggests
that PF4 does not attach to the “fingers” of the viral arm, but rather in some
way grabs it by the wrist and gets in the way of it getting a hold of the
handle. Or the knob for that matter, as the researchers have shown that PF4 can
affect both handle-pulling and knob-turning HIV strains. However, HIV virus
isolated from a small number of people seemed to be unaffected by PF4. And this
is another example of HIV diversity – most of the analysed strains are
inhibited by PF4, but some – are not.
The research is interesting for a few reasons. Firstly, it
identifies an important part of the HIV “arm” – the wrist. Much research has
been focused on the fingers or the handles/knobs as it is them that interact
with each other directly. It was interesting to see how grabbing the wrist can
also significantly affect the ability of the virus to open the doors. Secondly,
as the authors point out, PF4 not only binds the viral arm, but also activates
the immune system cells, which might in turn further facilitate fending off the
virus. Thirdly, identifying a new way by which body’s own proteins interfere
with viral infection can open some doors to development of new drugs. And
finally, as mentioned before, it further highlights the diversity of HIV, as
there was a small number of patients whose virus did not seem to have been
affected by PF4. This in turn further underlines the fact that, unlike for many
other viruses, HIV therapy should be personalised to the behaviour of the
particular strain infecting the particular patient.
1. Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor.
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