HIV & AIDS II

phenomenally high

Mutation Rate of replicating HIV is

3

How many mutations per cell division?

treat

The mutations are a huge part of why HIV is hard to

1

About _ mutation every time HIV replicates

everyday

On average every possible mutation at every position in the HIV genome is predicted to occur

flu season

There is more genetic diversity within a single HIV+ individual than an entire

massively diverged

Since the start of the HIV-1 group M pandemic (early 1900s) HIV sequences have

Consequences for how our immune system is going to respond, Important consequences for antiviral therapy

HIV-1 genetic diversity globally is HUGE

Can quickly gain resistance via adaptation

What are the consequences of mutation on antiviral therapy?

host cell chromosomes

Retroviruses stably integrate their DNA into

life of the cell

Once integrated the virus remains for the

Persistance, Latency

What are the important consequences of integration?

Persistance

infection is not easily cleared because there is a long-lived reservoir of infected cells

latency

integrated, but silent proviruses are not seen by the immune system

cell division

Cells that are infected pass these genomes onto daughter cells during

chronic

HIV is

HIV Viral Lifecycle Part, Assembly & Release

1. The integrated provirus directs the creation of

new RNA viral genomes (by transcription) and

new viral proteins (by translation)

2. HIV Protease cuts up a precursor protein (e.g.,

Pol) into its smaller functional proteins (e.g.,

reverse transcriptase, protease, integrase)

3. New viral particles are then assembled and

then are released from the cell to infect new

cells (“budding”)

protease

HIV virions are not infectious until they are processed by

acute, chronic

HIV infection has 2 stages:

virus

During the acute phase there is lots of

stabilize

after the acute phase the virus is able to

flu-like symptoms, 2 to 4 weeks after infection, Lasts for a few days or a few weeks

Acute HIV infection

50-90%

How many people with acute HIV experience flu-like symptoms?

severe immunodeficiency → AIDS (opportunistic infections)

Chronic infection

normal

For many years the CD4 levels are relatively

direct killing by virus, immune mechanisms

CD4 T cells are lost during HIV infection in 2 ways

8-12

Around ____ years of infection CD4 cells begin to go away

crash

When the CD4 cells are dwindling your whole immune system starts to

helper CD4 T cells

AIDS is a disease of

acute infection & chronic infection

The immune system is damaged during

chronic, progressive

In untreated people, the virus is ______ and the disease is __________

opportunistic infections

Destruction of the immune system leads to

cleared (even with therapy)

Latency is the key reason why virus is not

master conductors

CD4 T-cells are the ______ __________ of the immune system

Help B-cells make antibodies, Allow the recruitment and activation of innate immune cells, Help CD8 T-cells (cytotoxic T-lymphocytes)

What do CD4+ T cells do

controlled and reaches a low level

in the chronic phase Viremia is

virus/immune responses kill them

in the chronic phase the Number of CD4+ T cells slowly declines as

immune system begins to fail

in the chronic phase CD4+ T cells reach low enough level that the

further loss of proper immune system function and opportunistic infections

in the chronic phase the Virus replicates out of control resulting in

CD4+ T cell infection → CD4+ T cell death (infection & immune system) → CD4+ T cell replacement → repeat

CD4 T cell decline is gradual and involves a cycle of

severe immunodeficiency

Eventually… immune exhaustion and immune system ‘collapse’ which is called

adaptive immune system

AIDS is the result of depleted CD4+ T cells and a severely

compromised

disease outcome

The amount of virus at the set point predicts

immunosuppression

AIDS is an extremely severe form of

AIDS

Opportunistic Infections are common when chronic HIV

infection progresses to

weakened immune systems

Opportunistic infections occur in people with

TB

__ is the leading case of death globally among people living with HIV

• High prevalence in the same parts of the world

• Opportunistic infection

• Tb killed a lot of people with hiv bc hiv activated latent tb in the patient

  • Happens when CD4 rate comes down

Lethal synergy between HIV and TB