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<title>HPV infection — how E6 and E7 dismantle both brakes</title>
<desc>Cards covering how HPV takes over the cell, how E7 attacks RB, how p16 becomes the HPV-positive marker, how E6 attacks p53, and why HPV destroys the proteins rather than mutating the genes.</desc>
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<text x="30" y="36" font-size="20" font-weight="700" fill="#23303A">HPV INFECTION — the virus dismantles both brakes</text>

<!-- Overview -->
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<text x="48" y="88" font-size="15" font-weight="700" fill="#B3402F">HOW HPV TAKES OVER</text>
<text x="48" y="116" font-size="12.5" fill="#23303A">The HPV virus infects a human cell and slips in its viral genes.</text>
<text x="48" y="138" font-size="12.5" fill="#23303A">It gets the cell's own machinery to read those genes and build the proteins they code for —</text>
<text x="48" y="160" font-size="12.5" fill="#23303A">two of which are E6 &amp; E7 ("E" = early). The human cell builds the proteins HPV wants.</text>
<text x="48" y="186" font-size="12.5" font-weight="600" fill="#23303A">E7 → attacks the RB brake.        E6 → attacks the p53 guard.</text>

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<!-- E7 attacks RB -->
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<text x="48" y="270" font-size="15" font-weight="700" fill="#B3402F">HOW E7 ATTACKS RB</text>
<text x="48" y="298" font-size="12.5" fill="#23303A">RB has a "pocket" it uses to grip E2F.</text>
<text x="48" y="318" font-size="12.5" fill="#23303A">E7 carries a grappling hook shaped to fit that</text>
<text x="48" y="336" font-size="12.5" fill="#23303A">same pocket.</text>
<text x="48" y="358" font-size="12.5" fill="#23303A">E7 grabs RB exactly where RB grabs E2F →</text>
<text x="48" y="376" font-size="12.5" fill="#23303A">E2F is pried off and freed.</text>
<text x="48" y="398" font-size="12.5" fill="#23303A">Then E7 recruits the cell's disposal machinery</text>
<text x="48" y="416" font-size="12.5" fill="#23303A">and marks RB for destruction — sent to the shredder.</text>

<!-- E6 attacks p53 -->
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<text x="498" y="270" font-size="15" font-weight="700" fill="#B3402F">HOW E6 ATTACKS p53</text>
<text x="498" y="298" font-size="12.5" fill="#23303A">E6 recruits a host enzyme called E6AP (a</text>
<text x="498" y="316" font-size="12.5" fill="#23303A">tagging enzyme).</text>
<text x="498" y="338" font-size="12.5" fill="#23303A">E6 + E6AP latch onto p53 and tag it for</text>
<text x="498" y="356" font-size="12.5" fill="#23303A">destruction.</text>
<text x="498" y="378" font-size="12.5" fill="#23303A">The cell can no longer halt, repair, or self-destruct.</text>
<text x="498" y="400" font-size="12.5" fill="#23303A">Damaged cells survive and keep dividing →</text>
<text x="498" y="418" font-size="12.5" fill="#23303A">mutations and genome instability pile up.</text>

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<!-- p16 marker -->
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<text x="48" y="486" font-size="15" font-weight="700" fill="#3A6B7E">p16 BECOMES THE HPV+ MARKER</text>
<text x="48" y="514" font-size="12.5" fill="#23303A">Normally, active RB keeps p16 low (a feedback loop).</text>
<text x="48" y="534" font-size="12.5" fill="#23303A">Lose RB → that feedback is gone → p16 piles up.</text>
<text x="48" y="554" font-size="12.5" fill="#23303A">But the p16 is useless now: with RB already</text>
<text x="48" y="572" font-size="12.5" fill="#23303A">destroyed, it has nothing left to protect.</text>
<text x="48" y="600" font-size="12.5" font-weight="700" fill="#3A6B7E">High p16 (gene CDKN2A) = the HPV+ marker we measure.</text>

<!-- why not mutate -->
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<text x="498" y="486" font-size="15" font-weight="700" fill="#23303A">WHY HPV DOESN'T MUTATE THE GENES</text>
<text x="498" y="514" font-size="12.5" fill="#23303A">The TP53 and RB1 genes stay intact —</text>
<text x="498" y="534" font-size="12.5" fill="#23303A">HPV destroys the p53 and RB proteins directly.</text>
<text x="498" y="562" font-size="12.5" fill="#6E7F8C">By contrast, smoking-driven HPV− tumours</text>
<text x="498" y="580" font-size="12.5" fill="#6E7F8C">disable p53 the other way — by mutating the</text>
<text x="498" y="598" font-size="12.5" fill="#6E7F8C">TP53 gene itself.</text>

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