Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

microbiology > HIV infection > Flashcards

HIV infection Flashcards

1
Q

what is HIV?

A

HIV is a retrovirus, an RNA virus which uses reverse transcriptase (RT) to make a DNA copy that becomes integrated into the DNA of the infected cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

outline the characteritics of the HIV Genome Structure.

A
  • Small RNA virus (~ 10KB): expresses just 10 genes
  • Member of retrovirus family (uses reverse transcriptase to make DNA copy of itself)
  • Lentivirus - means its slow and characterized by long incubation period
  • has regulatory, structural and accessory genes
  • accessory genes help it t o overcome herd immunity
  • structural gene creates the viral capsid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

outline the Mechanism of viral replication of HIV.

A
  • GP160 on HIV allows it to dock onto the CD4 and CCR5 receptors on host cell
  • The capsid enters the cell and enzymes and nucleic acid are released
  • Using reverse transcriptase, single stranded RNA is converted into double stranded DNA
  • Viral DNA then is integrated into the cells own DNA by integrase
  • When the infected cell divides the viral DNA is read and proteins are made
  • the proteins are assembled
  • Budding of new immature virus
  • Immature virus breaks free to undergo more maturation
  • Maturation protein chains in the new viral particle are cut by the protease enzyme into individual proteins that combine to form a working virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what HIV gene is most targetted for treatments?

A

pol - this encodes reverse transcriptase, integrase and protease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

name the HIV primary and co-receptors.

A

primary = gp120 - binds to CD4 on T cell
- GP41
- GP120
co-receptors = CCR5 and CXCR4 chemokine receptors

CCR5 is prominant in early infection
- CXCR4 - later in infection - development of X4 strain mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the anti-retroviral therapy targets to target HIV replication?

A
  • integrase inhibitors
  • protease inhibitors
  • reverse transcriptase inhibitors
  • fusion / entry inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are the characteristics of HIV which allows it to mutate rapidly?

A
  • Error-prone replication (the enzyme reverse transcriptase makes at least 1 error in every replication cycle)
  • Rapid viral replication (generation time ~2.5 days)
  • Large population sizes (~1010 new virus particles produced each day)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are the clinical features of untreated HIV-1?

A

Vaginal/oral candidiasis
skin disease
fatigue
bacterial pneumonia
herpes zoster
oral hairy leukemia, thrush, fever, diarrhoea, weight loss
Kaposi’s sarcoma, non-Hodgkin’s lymphoma
Pneumocystis carinii pneumonia
Toxoplasmosis, oesophageal candidiasis, cryptococcosis
cns lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

outline HIV pathogenesis

A
  • HIV is integrated into the DNA of the infected CD4-expressing cells
  • HIV infects a range of CD4, helper T, dendritic cells, macrophages and thymocytes cells
  • evades antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why does the immune response to HIV-1 fail to clear the virus?

A
  • The immune system generates a massive immune response involving up to 20% of all circulating T and B lymphocytes
  • neutralising antibodies take months to develop - rarely neutralise the HIV strains
  • CD4+ T-helper response is lost because these are infected first
  • vigorous response from cytotoxic CD8+ but ultimately fail when “immune exhaustion” sets in
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

when antibodies are created for HIV antigens, why do these not completely neutrilise the virus?

A
  • surface is derived from the host cell membrane
  • spike is heavily glycosylated (with sugars resembling human types)
  • spikes either in deep pockets overhung by sugar molecules or only revealed when the virus docks onto the CD4 molecule
  • The envelope (gp120/41) proteins can change
  • virus can evolve to avoid antibody recognition
  • the circulating neutralising antibodies rarely recognise their own viral envelope variants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

cytotoxic t-cell role in the control of HIV-1

A
  • Cytotoxic T-Lymphocytes (CTL) appear early in HIV infection, coincident with a rapid drop in viral load
  • Depletion of CD8+ T-cells leads to marked rise in viral load
  • CTL causes HIV-1 to mutate different varients to evade immune system
  • CTL selection leads to HLA-class I associated “foot-prints” on viral evolution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does HIV-1 evade the CTL response ?

A
  • Mutant HIV variants that evade the T-cell response appear within weeks of HIV infection
  • Initially responses develop to the new variants, but these are undermined by the failure of CD4+ cell and dendritic cell function
  • HIV-1 nef protein - reduces cell-surface expression of HLA class I molecules, on the virus, needed for CTL recognition,
  • upreg of the “death” molecule Fas that can kill virus-specific CTL
  • HLA- A and B molecules are down-regulated to undermine CTL killing of infected cells but HLA-C expression is maintained to prevent NK cell killing
  • Ultimately CTLs develop functional “exhaustion”, associated with expression of inhibitory molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Summary of immune response to HIV

A
  • Vigorous immune response but no demonstrable protective immunity with rare exceptions
  • Excessive immune activation which favours viral replication
  • Immunological dysfunction with involvement of all elements of host defence
  • Ongoing viral replication with progressive immunological impairment leading to clinical manifestations of immunodeficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is life expectancy still reduced in HIV-infected people on cART?

A
  • Issues of adherence, side-effects, drug resistance
  • Increase in non-AIDS-defining illnesses (NADIs): lung, cardiovascular and renal disease
  • Incidence of NADIs is related to:
  • Size of latent HIV reservoir
  • Persistent immune activation
  • CMV co-infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

ART controls HIV replication but a viral reservoir persists, explain.

A
  • Even with the most effective available ART, a poorly-defined reservoir of latently-infected cells persists for years, and HIV starts replicating again (to pre-treatment levels) within weeks of cessation of therapy
  • HIV is thought to persist as DNA integrated into “resting” transcriptionally-silent CD4+ T-cells and other cells such as tissue macrophages and T follicular helper cells
  • HIV may continue replicating in lymphoid tissue and other immune-privileged sites
  • Reservoir size correlates with persistent immune activation, largely driven by translocation of microbial products across the gut (damaged gut-associated lymphoid tissue and leaky gut since primary infection)
17
Q

outline the whole process of how HIV invades the immune system.

A
  • HIV binds to CD4 receptor or co-receptor CCR5 or CXCR4
  • HIV fuses with cell membrane and reeases its genetic material into it
  • reverse transcriptase converts the rna into dna
  • the now viral dna goes into the host cells genome using integrase
  • the infected cell produced HIV particles, leading to cell destruction
    cell destruction:
  • Direct viral destruction of CD4+ T cells.
  • Indirect mechanisms, such as immune-mediated killing of infected cells.
  • Chronic immune activation leading to exhaustion and apoptosis of uninfected CD4+ T cells.
  • due to the loss of CD4 cells - the immune system lacks the same ability to combat infections and cancers
  • persistant activation of the immune system occurs due to ongoing viral replication and contributes to immune exhaustion
  • can lead to aids - CD4+ T cell count below 200 cells/µL
18
Q

outline the tests used to diagnose hiv.

A

antibody test:
- detects antibodies produced in response to hiv
- may not detect recent exposures 3-12 weeks

antigen/antibody combination tests:
- detects HIV antibodies and the p24 antigen produced by HIV
- detectable after 2-4 weeks

nucleic acid tests (NAATs)
- detects viral rna in blood
- can identify hiv after 10-14 days of exposure
- most sensitive
- expensive

19
Q

outline the diagnostic testing process of hiv.

A

a. Initial Screening:

First Test: Typically an antigen/antibody combination test (lab-based or rapid test).
If positive, further testing is required to confirm the result.
b. Confirmatory Testing:

A second test is performed using a different method (e.g., HIV-1/HIV-2 differentiation assay) to confirm the diagnosis.
This process rules out false positives from the initial test.
c. Additional Testing:

HIV RNA Testing (NAT): Used when confirmation is needed or to detect acute HIV infection during the window period.
Western Blot: Historically used for confirmation but now largely replaced by modern tests.

20
Q

Describe how HIV is prevented.

A
  • use condoms
  • reduce number of sexual partners
  • regular testing

pre-exposure prophylaxis:
- medication for those with a HIV-positive partner
- reduces risk of aquiring HIV

post-exposure prophylaxis:
- short course of antiviral drugs taken within 72 hours of potential exposure to HIV

  • providing clean needles in drug programs
  • ensuring safe disposal of sharps and needles
  • education and awaereness
  • public health campaigns
21
Q

basic clinical features of HIV and aids

A

early/acute infection - 2-4 weeks:
- flu-like symptoms

chronic infection (clinical latency stage)
- can be assymptomatic
- persistant generalised swollen lymph nodes - Lymphadenopathy
- gradual decline in CD4 count
- diffuse symmetrical maculopapular rash

symptomatic HIV infection (CD4+ T cell count <500 cells/µL):
- Persistent fever
- Weight loss
- Chronic diarrhea
- Fatigue
- Night sweats
- Oral thrush (fungal infection in the mouth)
- Herpes zoster (shingles)
- Recurrent respiratory infections (e.g., sinusitis, bronchitis).

AIDS:
- Severe immune suppression leads to life-threatening infections and cancers.
eg
- Pneumocystis jirovecii pneumonia (PCP
- candidiasis
- cervical cancer

22
Q

Have a basic understanding of the global burden of HIV infection.

A

hella hella crazy

  • 38.4 million people globally are living with HIV.
  • Of these, approximately 1.7 million are children (under 15 years old).
  • 650,000 people died from AIDS-related illnesses in 2022, roughly 1 death every 49 seconds.
  • 67% of global HIV cases are in Sub-Saharan Africa.
23
Q

what 2 markers are used to monitor HIV infection?

A
  1. CD4 cell count
  2. HIV viral load
24
Q

what is Acute HIV Infection (acute retroviral syndrome - ARS) and its presentation. what is the peak viral load called?

A

the initial, acute infection of aids
catagorised with high viral load
- peak viral load - viremia

25
Q

when diagnosing someone with aids, they can develop certain conditions, what are some of these?

A
  • Pneumocystis pneumonia (PCP)
  • Severe oropharyngeal and oesophageal candidiasis
  • Kaposi’s sarcoma
26
Q

how do AVRs work?

A

ARVs work by interfering with the way that HIV virus replicates.
They do this by interfering with the docking of HIV and interfering with the action of major HIV enzymes
Reverse transcriptase
Integrase
Protease

27
Q

name the HIV treatments which work by fusion inhibition.

A

ENFURVITIDE
T-20

28
Q

name the HIV treatments which work by CCR5 receptor blocker.

A

MARAVIROC

29
Q

name the HIV treatments which work by non nucleoside reverse transcriptase inhibitor.

A

EFAVIRENZ
NEVIRAPINE

30
Q

name the HIV treatments which work by nucleostide reverse transcriptase inhibitor.

A

3TC LAMIVUDINE*
FTC EMTRICITABINE*
D4T STAVUDINE
AZT ZIDOVUDINE
TDF TENOFOVIR**
ABC ABACAVIR

31
Q

name the HIV treatments which work by protease inhibitors.

A

DARUNAVIR
ATAZANAVIR
LOPINAVIR
RITONAVIR

32
Q

name the HIV treatments which work by integrase inhibitors.

A

DOLUTEGRAVIR
RALTEGRAVIR
ELVITEGRAVIR
BICTEGRAVIR

33
Q

Importance of ART adherence

A

Need to aim for >95% adherence to minimize development of drug resistance
Cannot miss more than one dose per month of fixed dose combination ART
If viral load is maintained below level of detection, can assume vanishingly low risk of onward transmission (U = U)
Thus, ART has an important role in prevention (TasP)
Adherence in resource-limited settings may be hampered by infrastructure issues, e.g. stock-outs
Transmitted ART drug resistance is around 10 – 20% in most settings

34
Q

name the key populations where HIV prevelance is high.

A

sex workers and their clients
gay men and other MSM
people who inject drugs
transgender people
prisoners

35
Q

Early infant diagnosis of HIV infection

A

Most countries provide mass testing of infant dried blood spots before 6 weeks of age (using PCR)
Early diagnosis allows the rapid institution of ART, before long-term immune damage is sustained
Rapid reduction in infant viral load leads to smaller reservoirs and, often, low or undetectable antibody levels
?? Potential for infant cure

36
Q

Barriers to HIV-1 vaccine development

A

The traditional vaccine strategies used for other organisms (live attenuated or killed vaccines) are deemed too risky for HIV – although these approaches have been effective in some animal models
HIV-1 is highly variable – an effective vaccine would need to provide protection against the multiple variants of HIV present in each infected person, as well as against the distinct clades of HIV throughout the world (which differ by 10-30% from one another) –HIV diversity is increasing over time
A successful vaccine would also need to provide protection against HIV acquisition by different routes (genital/oral/intravenous/intra-uterine)
There is evidence of protective immunity in most infections for which we have a successful vaccine – but virtually everyone infected with HIV-1 will develop AIDS without treatment – so we don’t know if it is possible to generate protective immunity against HIV infection – or what is needed to do so

37
Q

Vaccine-induced generation of bnAb germline antibodies

A

Generation of bnAb precursors by sequential stimulation of selected (rare) B-cells that share B-cell receptor usage with VRC001: proof of concept shown in phase I trial Leggat, Science 2022
It is expected that, after initial vaccination, will need vaccination with a series of further immunogens for boosting and “polishing”

38
Q

what are the 2 types of HIV/

A

HIV-1 - most common - worldwide
HIV-2 - mainly found in west africa

microbiology (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions