24. HIV Flashcards
what type of virus is HIV?
as positive sense single stranded RNA retrovirus
what genus of retroviridae does HIV belong to?
lentivirus
what species does HIV infect?
Humans and primates
how many people have died as a result of HIV?
650 million
how many people are currently living with HIV?
40 million
what is the distribution of HIV?
uneven and changed over time
currently main effects southern Africa and low income countries
how many people contraced HIV in 2022?
over 1 million
what is HIV really ?
an umbrella term for different viruses HIV-1 and HIV-2
which HIV viruses is the pandemic strain?
HIV-1 group M and its subtypes
why are there so many groups of HIV?
natural evolution and origin events for each group of HIV
where do HIV-1 strains originate?
Chimpanzees and gorillas
where do HIV-2 strains originate?
Sooty mangabey monkey
what type of disease is HIV?
Zoonotic
what is the animal reservoir for HIV?
primates
how did cross species transmission occur in HIV?
due to the hunting of primates for food or keeping them as pets
Where do several of the HIV lineages come from ?
independant zoonotic infections
what is HIV-1 group M derived from?
SIVcpz from P.troglodytes (chimps)
what was the viral route HIV spread around the world?
emerged in the congo and then moved to haiti and the west coats of the USA
The virus got to Europe both from the USA and africa
why is the retrovirus membrane important?
for attachment and entry into the host cell
what does the retrovirus matrix do?
encloses the capsule and protects the genome
what are the 3 key enzymes in retroviruses?
Reverse transcriptase
Integrase
Proteases
what does reverse transcriptase do?
makes DNA from an RNA template
what does integrase do?
integrates the retrotranscribed viral DNA into the host genome and is the key to persistent infection
what do retrovirus accessory proteins do?
increase the infectivity of the virus usually as transcriptional activators
important for virus assembly
avoidance of the immune system
what is the final step in the viral life cycle?
cleavage of precursor proteins to activate them
what cells do HIV mostly infect?
CD4+ helper T cells
what does the virus binding to the CD4 receptor cause?
a conformational change in the the receptor that exposes the CCR5 co receptor
what is CCR5?
a CD4 co receptor that HIV also binds
what happens after CCR5 binding?
the virus enter the cell by fusing the membranes
what happens when the HIV viruses enters the t helper cell?
the viral membrane is degraded first and then the capsule degrades after it
what happens once the viral capsule is degraded?
the genome binds reverse transcriptase and makes DNA from the RNA
what can reverse transcriptase make from ssDNA?
DsDNA
what happens to reverse transcribed viral dsDNA?
it is bound by the integrase and taken into the nucleus through the nuclear pore
the integrase inserts the viral DNA into the host cell genome and the cell transcribes it as its own DNA
where are the early viral proteins transported?
to the cell membrane and they are inserted
what tend to be late viral proteins?
poly proteins made of several componenets - more complex virulence proteins
where do the final proteins and mRNA end up?
at the host cell membrane to form a virion
what is the final maturation step in the HIV life cycle?
key proteases activating the precursor proteins
what is the cellular tropism for HIV?
main target: CD4+ T cells
other targets: phagocytes and CNS
how does HIV spread around the body?
taken to the draining lymph nodes and then enters the bloodstream
what can develop as a result of HIV infection?
acquired immune deficiency syndrome or AIDS
when was AIDS first identified?
1981
what is the HIV virus related to?
the first isolated human retrovirus Human T cell leukaemia virus
where was HIV first isolated?
from a lymph node of a patient in Paris
what are the 2 markers for diagnosing HIV?
- how much viral mRNA is in the blood stream to indicate how much viral replication is occurring
- how many CD4+ T cells are in the blood to indicate how many cells are being killed
what happens to the T cell count during acute HIV infection?
initially goes down very quickly but the immune system can recover
what happens during a latent HIV infection?
a game of immune cat and mouse of HIV killing immune cells and then immune system recovering which can last for years
Ultimately the T cell count decreases
what happens when HIV comes out of clinical latency?
the threshold value of the amount of HIV per ml of blood is crossed and the immune system cannot control the infection.
T cell count decreases to the point of none left and death occurs
what are the key events in HIV disease progression?
- primary infection usually as an STI
- infect the gut due to close proximity and high vascularisation
- high levels of virus in plasma and dissemination to lymphoid organ
- chronic HIV infection of lymph nodes and depletion of CD4+ T cells
- chronic immune activation due to HIV
- accelerated virus replication and rapid CD4+ T cell turnover
- destruction of the immune system
how are CD4+ T cells killed during HIV infection?
- directly killed by the virus
- indirectly killed by immune exhuastion or other immune cells
how does HIV replication cause CD4+ dysfunction?
- causes high turnover of cell leading to immune exhaustion
- due to death of T cells the rate of T cell proliferation is accelerated as well as the rate destruction
what does the destruction of mature T cells and impaired production of T cell lead to?
AIDS
How is AIDS defined?
presence of terminal HIV-1 infection
CD4+ t-cell count of under ~200 cell /µl of blood
presense of opportunistic infections that otherwise wouldn’t be a problem
what does a lower CD4 T cell count mean?
higher likelihood of opportunistic infections that
results of infection is multi organ failure as the body cannot cope
what are a few common opportunistic infections in HIV patients?
brain - cryptococcal meningitis
lungs - TB and pneumonia
skin - herpes
genitals - gential herpes, HPV, yeast infections
what are the 2 types of different factors that effect progression to AIDS?
viral factors
host factors
what are host factors effecting AIDS progression?
HLA alleles
immune function
genetic polymorphisms
natural resistance to HIV
what are viral factors effecting AIDS progression?
defective viruses and genetic variability
type of HIV like HIV-2 can sometime cause AIDS but slower
what can make someone resistant to HIV?
modified or lack of CCR5 receptor so the virus doesn’t bind properly
what disease progression does heterozygous CCR5 mutation show?
delayed progression to AIDS
what disease progression does homozygous CCR5 mutation show?
Resistance to HIV that use that receptor like most HIV-1
what are long term non Progressor?
1-5% of the population get infected but never develop AIDS
they can help us know what defences are effective
Criteria:
10+ years of having HIV but not developing AIDS
low viral loads
immune cells remaining high
What is ART?
Antiretroviral therapy
what is ART used to do?
block retroviral replication at various different steps to prevent destruction of CD4+ T cells and disease progression
prevent transmission
what does ART target?
viral attachment
fusion
reverse transcriptase
integrase
protease cleavage
how does ART reduce transmission?
with no detectable viral replication the virus is not transmissible
Generally why does HIV transmission occur?
lack of knowledge or medical care
most transmission happens because people don’t know they have HIV
what is PrEP?
Pre-exposure prophylaxis
taken before HIV exposure
for people not yet infected but may lead a high risk lifestyle
What is PEP?
post-exposure prophylaxis
taken after HIV exposure to prevent developing infection
what are the WHO targets for HIV infections and treatments?
90% of people should be aware they are infected
90% of those aware should be on treatment
90% of those on treatment should have undetectable virus
Are we meeting WHO goals for HIV?
No despite many more people receiving treatment
what is a big problem in terms access to ART therapy?
the highest effected areas cannot afford or access ART treatment as the demand is higher then the supply
what happens when ART treatment stops?
the virus starts replicating again and the virus takes hold again
what is the limitation of ART?
it doesn’t treat the viral DNA already integrated into the host genome as it is too similar to distinguish
how does ART therapy need to be given?
for life
properly to prevent resistance to mutation
why don’t we have a HIV vaccine?
- due to the massive genetic diversity of HIV it is hard to find a single target
- we haven’t found a way to induce broad active antibodies that can neutralise the virus
how diverse is HIV?
very
1 person with an active HIV infection can have more viral diversity in their body then all known influenza strains
