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STEP Pathology > deck_4984085 > Flashcards

deck_4984085 Flashcards

1
Q

What are the two types of HIV?

A

•HIV-1 (major cause of AIDS worldwide)•HIV-2 (found primarily in West Africa and Asia)

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2
Q

HIV is a member of what viral family? Properties?

A

Retroviridiae•Human lentiviruses nononcogenic, cytopathic retroviruses–Properties include:a) Life-long persistence.b) High mutation rate.

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3
Q

What are the three stages of HIV infection?

A

1) Acute phase - rapid viral replication and dissemination throughout body.2) Asymptomatic (latent) phase- virus is brought under control by immune system.3) Symptomatic infection- Immune failure, opportunistic infections, AIDS-related cancers.

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4
Q

What are the primary genetic groups of HIV-1? Subgroups?

A

a) M = main or major.b) O = outgroup (or outlier)c) N & P = minor subgroups found only in Africa.–Further divided into nine genetic subtypes (or clades) designated A through I.•Based on degree of sequence diversity within the gag and envelope genes.•Clade B is most prevalent in U.S. and Europe.

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5
Q

How else is HIV categorized?

A

–No clearly defined serotypes, but viruses are further defined by:a) Co-receptor utilization (CXCR4, CCR5, etc); previously called “M-tropic or T-tropic”.b) Syncytium-inducing capability–NSI = non-syncytium inducing–SI = syncytium-inducing.

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6
Q

Describe the virion structure of HIV.

A

virions are spherical-shaped, enveloped particles with:-cylindrical inner core-enzymes required for replication-envelope containing viral glycoproteins

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7
Q

What does the cylindrical inner core contain?

A

-two copies of viral RNA genome (noncovalently bound at 5’ end)- core composed of capsid protein (p24)- used in diagnosis and virus detection

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8
Q

What kinds of enzymes does HIV need to replicate?

A
  • reverse transcriptase- integrase- protease
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9
Q

What are some important virally derived envelope glycoproteins in HIV?

A

gp120 - receptor binding.gp41 - membrane fusion activity.

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10
Q

Describe the HIV genome.

A

-10kb-flanked by two long-terminal repeats (LTRs)

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11
Q

What do LTRs do?

A

viral promoters for mRNA synthesis and genome replication.

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12
Q

What do the gag protein (group-specific antigen protein), expressed as myristoylated precursor (pr55) get cleaved to?

A

nucleocapsid (p7) - binds RNA genome•capsid (p24) - forms cylindrical core•matrix (p17) - lines inner surface of viral envelope.

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13
Q

What is pol cleaved to produce?

A

pr170 gets cleaved to yield:-reverse transciptase-protease (p11)-integrase (p32)

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14
Q

How is pol expressed?

A

as gag-pol precursor protein (pr170) via -1-ribosomal frameshift

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15
Q

How are envelope proteins expressed?

A

as a glycosylated precursor (p160) which gets cleaved by cellular proteases to yield p120 and p41

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16
Q

What are some accessory proteins unique to HIV?

A

-tat-rev-nef, vpr, vpu, vif (nonessential, contribute to pathogenesis)

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17
Q

What is tat?

A

transactivator of transcription- enhances rate of transciption

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18
Q

What does rev do?

A

affects mRNA transport out of nucleus and facilitates transport of unspliced mRNAs.

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19
Q

What is the primary receptor for HIV attachment?

A

CD4

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20
Q

What other receptors are needed for HIV entry?

A

CCR5 and CXCR4

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21
Q

Where is CCR5 found? What is it the receptor for?

A

macrophages; receptor for RANTES, MIP-1

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22
Q

What isCXCR4 the receptor for?

A

SDF-1 (found on T-cells and others)

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23
Q

Once a double stranded DNA genome is made via reverse transcriptase, what happens to it?

A

its integrated into the host chromosome via integrate. When inserted, it is called a provirus

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24
Q

T or F. HIV integration does not require cell division

A

T. Unique

25
Q

What happens following integration?

A

viral genes are expressed- divided into early and late phases

26
Q

What does gene expression begin with?

A

synthesis of full-length RNA copy of prevail DNA from LTR that is spliced into mRNA for regulatory proteins (tat, rev, nef)

27
Q

What does tat do?

A

binds to TAR to increase transcription

28
Q

What does rev do?

A

mediates transition from early to late gene expression and allows for structural proteins to be made. Rev binds to RRE (Rev Response Element) and facilitates nuclear export unspliced mRNAs. In the absence of Rev, singly spliced and unspliced mRNAs are not transported from the nucleus to the cytoplasm.Unspliced mRNAs encode viral structural proteins.

29
Q

When does assembly occur?

A

once gag, gag-pol, and env (structural) proteins are synthesized

30
Q

What are the three steps of assembly?

A

-packaging of RNA genome into a core-release of particles by budding-‘Maturation’-cleaving of core proteins by protease

31
Q

What are the routes of transmission for HIV?

A

-direct sexual contact-blood and blood products-perinatally

32
Q

What are some body fluids that contain significant amount of HIV?

A

-semen-breast milk-cervical secretions

33
Q

What are some body fluids that do not contain significant amount of HIV?

A

-urine-saliva-tears-cerebrospinal fluid*Risk of seroconversion after accidental needle-sticks by health-care workers is ~0.3%

34
Q

What the symptoms of an acute primary infection?

A

-fever-malaise-diarrhea-LAD-headacheoccurs 3-6 wks after infection

35
Q

T or F. During the acute primary infection virus-specific immune response can be detected (both humoral and CMI)

A

T, Usually detectable antibody responses don’t appear until 3 months after initial infectionthis stage is characterized by high-level viremia

36
Q

T or F. During the asymptomatic stage (6-12 yrs) the virus is replicated quickly still

A

T. Estimated that 10^10 virus particles are produced and 10^9 CD4+ T cells are killed each day.

37
Q

What is AIDS defined as?

A

CD4 below 200/mm^3

38
Q

What are two criteria used to predict disease progression?

A

a) Correlation between CD4+ T cell count and risk for progression.b) Strong correlation between viral load and disease onset–62% with high virus loads (~36,000 copies/ml of plasma) developed AIDS within 5 yrs.–Only 8% with low loads (~4000 copies/ml) developed AIDS in 5 yrs.

39
Q

T or F. Although most infections eventually lead to clinical disease (symptomatic infection), ~5% - 10% of HIV-infected individuals do not show disease progression and do not develop AIDS.

A

T. These people are called “elite controllers” aka long-term non-progressorsRemain symptom-free, maintain plasma virus levels of

40
Q

What could be responsible for ‘elite controller’ immunity?

A

over-expression of MHC-1 (HLA-B 57)

41
Q

What other changes can reduce the development of the disease?

A

-mutations in CCR5-Nef-deletion mutations

42
Q

What mutation most commonly disrupts the function of CCR5 (good for us)?

A

Delta32 base pair deletion that introduces a premature stop codon

43
Q

T or F. Homogeneous Delta32+ people are completely resistant to HIV

A

T.

44
Q

T or F. Heterozygous Delta32+ people are completely resistant to HIV

A

F, but they do show delays in disease progression of ~2 yrs.common in European whites

45
Q

What are the basic approaches to diagnosing HIV?

A
  • antibody detection assays- nucleic acid detection (HIV RNA or integrated provirus)
46
Q

What antibody detection tests are available?

A
  • ELISA- Western Blot- 4 FDA approved rapid tests
47
Q

What antigen is ELISA looking for?

A

p24 (used to detect anti-HIV antibodies in the patient’s serum)

48
Q

What antigen is Western blot looking for?

A

-confirmatory test-need reactivity to both p24 and gp120 to be positive

49
Q

What are some methods available for nucleic acid detection?

A
  • PCR- RT-PCR (reverse transcription PCR)- bDNA assay (branched)
50
Q

What is PCR used to do?

A

quantitate amount of provirus in circulating lymphocytes

51
Q

T or F. PCR will detect non-replicating (latent) provirus

A

T. as well as provirus in cells actively producing HIV

52
Q

What is RT-PCR used for?

A

to quantitate viral RNA levels in plasma

53
Q

What are bDNA assays used for?

A

uses hybridization (not PCR) with a highly branched, labeled DNA probe to quantify RNA levels in blood (very sensitive)

54
Q

*Direct virus isolation can be performed, but is typically not used because sufficiently high titers in the serum are seen only very early (during acute phase) or late when symptomatic disease is evident.

A

*Direct virus isolation can be performed, but is typically not used because sufficiently high titers in the serum are seen only very early (during acute phase) or late when symptomatic disease is evident.

55
Q

What is the purpose of all HIV therapy?

A

to reduce viral load since there is good correlation between viral load and disease progression

56
Q

What pre-exposure prophylaxis is available for HIV? option 1

A

A combination of two anti-retroviral drugs (tenofovir and emtricitabine; also known as Truvada) that is taken by individuals who are not infected with HIV, but who are at high risk for infection.Tablet (pill) that must be taken every day. PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by more than 90%.

57
Q

What pre-exposure prophylaxis is available for HIV? option 2

A

Vaginal microbicide gel containing tenofovir (may not be very effective)

58
Q

Why is vaccine development against HIV so challenging?

A

immune evasion is a hallmark of HIV:– HIV proteins mask their neutralizing sites– HIV-1 proteins down regulate T cell immune response to the virus– Antigenic diversity results in escape from both neutralizing antibodies, as well as CD8+ and CD4+ T cell responses

59
Q

What are some requirements for an ideal HIV?

A

Induce cellular and humoral immune responses against virus-infected cells as well as HIV– Elicit neutralizing antibodies to bind up free virus in body secretions– Induce antibodies that neutralize and do not enhance HIV infection– Induce local immunity at all entry sites for HIV– Produce T cell memory to eliminate HIV infected cells• Not induce autoimmune responses• Safe with long-lasting effects

STEP Pathology (80 decks)

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