MIC 201 test 1 lecture 2 Flashcards

• HIV is enveloped virus (membrane)
• most viruses are enveloped (covid, flu, etc.)
• membrane must fuse w/ membrane that encloses our cell
• must fully fuse w/ cell it wants to infect

specific interactions btw HIV gp120 protein and T-cell CD4 for initial attachment of HIV to T cell

-> and then subsequently CCR5 (coreceptor) that is required for membrane fusion

gp120 protein is on surface

• viral protein (on HIV) responsible for attaching to cell + getting membranes to fuse
• 2 steps:
  1. initial attachment
  2. subsequent infusion
• gp120 evolved to bind to CD4 (high affinity, bind tightly) = HIV tethers to cell
• upon contact, gp120 change structure to bring viral particle closer to cell surface (reorganization means proteins become much closer)
• gp120 also binds coreceptor AFTER binding to CD4
• these 2 (gp120 to CD and to coreceptor) = drive fusion of the cells

gp120 +CD4, reorganization of gp120 + coreceptor binding -> membrane fusion = now complete membrane fusion

early phase done when DNA incorporate into host cell chromosomes = late phase

in late phase

• replicate self: genes expressed into RNA and -> viral proteins = forms progeny virus (new viruses

...

cut up by the HIV protease (OR) into their individual components

• during late phase of infection cycle, HIV proteins (including reverse transcriptase and integrase) are initially made as "beads on a chain" that have to be freed from one another (protease, scissor, cuts it) to become functional

protease

in order to make infective virions

infective virions.

many types of cells, but particularly infects CD4/coreceptor cells very easily

1981

reported 5 young men had unusual infection. There were clusters of unusual/uncommon cases being reported.

1981

1st global indication of HIV
June 5

• June 5, CDC published weekly report describing cases of rare lung infection, PCP (pneumocytis carinii pneumonia) in 5 young, previously health, gay men
• all the men had other unusual infections
• this indicated their immune systems were not working
• first official reporting of what would become known as AIDS epidemic

June 6

• doctors around US flood CDC w/ reports of similar uncommon cases (opportunistic infections)

these indicated problems with immune systems (suspected issue)

• confirmed later that year, study published saying 4 patients suffering from infection analyzed, reported that LEU3 (T helper cells) were MUCH lower (0 or almost 0) than healthy individuals (42 ish), and other immune cell levels were also very low
• indication of immune system issue, realized it was t helper cells (CD4+ cells)

end of 1981

• now knew what was going on w/ immune system
• still no idea what was causing disease
• took 2 years to find out what was causing immunosuppression
• partially bc retroviruses were discovered recently (in 70s). They were new and didnt know many human diseases caused by them. they did not expect it to be caused by retroviruses

3 initial hypotheses

link doesnt work

https://jamanetwork.com/learning/audioplayer/16634751?widget=personalizedcontent&previousarticle=16653636

1983 breakthrough

isolated it

removed blood from person w/ HIV, cultured, visualized cells, saw the HIV virions emerging from cells (see budding in picture)

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2008/barre-sinoussi-bio.html

• 1892, meetings about how observations suggestion disease attacked immune cells, but strong depletion of CD4 lymphocytes greatly hindered isolation of virus from rare cells in patient with AIDS
• lymph node biopsy from patient w/ lymphadenopathy
• waited until new year to obtain first patient biopsy from which lymphocytes isolated + cultured
• tested for reverse transcriptase activity
• detected weak enzymatic activity which increased significantly a few days later
• reverse transcriptase activity level dropped dramatically as T lymphocytes were dying
• added lymphocytes from blood donor to cell culture -> virus started to infect newly added lymphocytes + detected reverse transcriptase activity again
• named newly isolated virus: lymphadenopathy associated virus (LAV)
• isolated, amplified, characterized
• ...

• HIV is the infectious agent (virus)
  • causes slow decline of immune system
• AIDS - end stage of HIV infection when a characteristic spectrum of opportunistic infections or cancers takes advantage of the weakened (or eroded) immune system

human immunodeficiency virus

the infectious agent (virus)

causes slow decline of immune system

acquired immunodeficiency disease syndrome

AIDS - end stage of HIV infection when a characteristic spectrum of opportunistic infections or cancers takes advantage of the weakened (or eroded) immune system

having HIV does NOT mean necessarily have AIDS

now, most ppl dont have AIDS anymore

• mostly about elimination of CD4+ lymphocytes (T helper cells)

Red – level of HIV in blood

- infected -> viral levels very high (acute phase)

- feels like bad flu

- eventually, if immune system working well, bring down infection

- don’t get rid of phase

- individual enter asymptomatic phase (clinical latency) - no signs of infection

- person feels normal

- asymptomatic stage can last years

Eventually, person becomes susceptible to many types of infection

- opportunistic pathogens -> pathogens that don’t normally hurt if have good functioning immune system

- types of diseases first described. The unusual infections found bc their immune systems were low

Ppl succumb to opportunistic infections

HIV = primary infection -> leads to secondary (opportunistic) infections that are the cause of death

Untreated – can last 4/5 years

Blue – levels of T helper cells

- normal – 1000 cells/million cells

- intial drop during acute phase = normal
- but CD4 counts do NOT return to normal after acute phase

- in diff individuals, have diff levels after acute phase. Higher the better

- usually return to level that allows immune system to be relatively normal

- over years, levels drop bc the cells are targeted by HIV

Aids = acquired immune deficiency syndrome

Syndrome – disease state, grouping of symtpsoms

Use bc individuals can die of different things (depends on particular opportunistic infection)

group of symptoms that consistently occur together or a condition characterized by a set of associated symptoms

• if erase these, reduce effectiveness of other immune cells
• Tregs
  • suppresses tumor immunity
  • promotes immune intolerance
  • maintains lymphocyte homeostasis
• Th1
  • promotes tumor immunity
  • intracellular pathogens
  • drives autoimmunity
• Th2
  • extracellular pathogens
  • allergy
  • asthma
• Th17
  • controversial tumor immunity
  • breaks immunity tolerance
  • extracellular bacteria
  • autoimmunity

https://www.aids.gov/hiv-aids-basics/staying-healthy-with-hiv-aids/potential-related-health-problems/opportunistic-infections/

“HIV is certainly character-building. It’s made me see all of the shallow things we cling to, like ego and vanity.

Of course, I’d rather have a few more T-cells and a little less character.”