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MI Immuno/Heme > Human Retroviruses > Flashcards

Human Retroviruses Flashcards

1
Q

HIV viral type

A

Enveloped, diploid +ssRNA

Because it is enveloped, HIV is easily inactivated by drying, detergents, EtOH, bleach, and formaldehyde

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2
Q

HIV glycoproteins required for attachement and entry into host cell

A

gp120 and gp41

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3
Q

What capside protein do many lab tests use to detect HIV?

A

p24

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4
Q

Long terminal repeats (LTRs) in HIV genome

A

Contain promoter sequences and controls expression of viral genes

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5
Q

HIV VAP

A

gp120 attaches to CD4

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6
Q

HIV co-receptors required for infection of macrophages

A

CCR5

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7
Q

What chemokine receptors are expressed and required for HIV to infect all CD4+ T cells

A

gp120 binds to

CD4
co-receptors:
CCR5
CXCR4

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8
Q

What HIV protein fuses the viral enveloped to the host cell membrane

A

gp41

gp120-chemokine receptor binding then induces a conformational change in gp41 - causing fusion

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9
Q

Unlike most RNA viruses, HIV replicates where?

A

In the host nucleus

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10
Q

What results in the extensive antigenic drift seen in HIV?

A

HIV RT enzyme is error prone and makes lots of mistakes during replication

This = extensive antigenic drift in the gp120 gene, antigenic variation in the gp120 protein, and consequently, rapid generation of drug-resistant mutants

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11
Q

HIV is tropic for what cells?

A

CD4+ T cells and macrophages

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12
Q

Macrophage-tropic HIV strains

A

R5 viruses that require CD4 and CCR5 to enter host cells and preferentially infect macrophages and CCR5+/CD4+ T cells

Most abundant early in infection

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13
Q

T-cell tropic HIV strains

A

X4 viruses

Require CD4 and CXCR4 to enter host cells - preferentially infecting CXCR+/CD4+ T cells

Predominate later in infection

Leads to massive reduction in T cells and immunodeficiency (AIDS)

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14
Q

First three months after HIV infection

A

Viremia - disseminated throughout body

Concomitant transient decline in circulating CD4+ T cells (primarily CCR5+/CD4+ T cells)

Reduction at the end of this period coincides w appearance of neutralizing Abs

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15
Q

HIV when CD4+ T cells fall below 200/µL

A

AIDs

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16
Q

HIV resistant individuals

A

Remain uninfected despite long-term HIV exposure

Typically homozygous for CCR5 mutations

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17
Q

HIV-1 epidemiology

A

Found outisde of Africa

N/S America, Asia, and Europe

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18
Q

HIV-2 epidemiology

A

Primarily found in central Africa

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19
Q

HIV transmission

A
  1. Blood-to-blood (parenteral) transmission
  2. Sexual transmission
  3. Perinatal transmission
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20
Q

Average time elapsed between HIV infection and AIDS

A

7 years

varies from 2 to > 10 years

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21
Q

Acute retroviral syndrome

A

Can occur 2 wks to several months after initial infection

Flu-like or mononucleosis-like sxs

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22
Q

Herald diseases of HIV

A

Toxoplasma gondii brain abscess w/ multiple ring-enchancing lesions

Crptosporidium GI infection

Candida albicans oral and esophogeal infection
Pneumocytsis jiroveci pneumonia
Cryptococcus neoformans meningitis

Mycobacterium avium-intracellulare
Mycobacterium TB

CMV reactivated infection (especially CMV retinitis)
JC virus reactivation
EBV reactivated infection
Hep C
HHV-8

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23
Q

What causes Kaposi’s sarcoma

A

HHV-8 infection - strong indicator of HIV infection

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24
Q

What herald disease in HIV Pt causes hairy luekoplakia in the tongue and CNS B cell lymphomas

A

EBV reactivated infection

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25
Q

What herald disease causes chronic diarrhea and weight loss in HIV+ Pt?

A

Cryptosporidium GI infection

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26
Q

What herald disease causes HA, focal neurologic deficits, NV, and seizures in HIV+ Pt?

A

Toxoplasma gondii brain abscesses w/ multiple ring enhancing lesions

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27
Q

What encapsulated yeast is considered a herald disease in HIV Pt?

A

Cryptococcus neoformans meningitis

Seen by India ink stain of CSF

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28
Q

Nucleoside/tide Analogue RT inhibitors used in HIV Tx

A

Zidovudine

Abacavir

Emtricitabine

Tenofovir

Lamivudine

Phosphorylated by the host and cause DNA chain termination during reverse transcription

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29
Q

Side-effects of NRTIs

A

Bone marrow suppression

Pancreatitis

Peripheral neuropathy

Myopathy

Potentially fatal lactic acidosis w/ hepatic steatosis

30
Q

What NRTI is contraindicated in Pt’s with HLA-B*5701 polymorphism?

A

Abacavir - increased risk of severe hypersensitivity reactions

31
Q

What should Pt be screened for before Tx w/ Abacavir for retroviral therapy?

A

HLA-B*5701 polymorphisms

32
Q

Non-nucleoside analogue reverse transcriptase inhibitors used in Tx of HIV

A

Directly bind to HIV RT and inhibit its activity

Dorvirine

Efavirenz

Etravirine

Nevirapine

Rilpivirine

Used for systemic Tx of HIV-1 only (HSV-2 has intrinsic resistance)

33
Q

Side-effects of NNRTIs

A

Rash (SJS - type IV hypersensitivity rx’n)

Hepatotoxicity

CNS sxs (abnormal dreams, delusions etc.)

34
Q

What NNRTI is known for CNS side-effects

35
Q

What enzyme metabolizes NNRTIs

A

CYP450 enzymes

36
Q

What HIV drugs prevent maturation of viral proteins and production of mature, infectious, virions

A

Protease inhibitors (PIs = -navir)

Atazanavir

Darunavir

Lopinavir

Ritonavir

37
Q

Side-effects of protease inhibitors used in HIV Tx

A

Increased trigs and LDL

Insulin resistance

38
Q

Ritonavir boosting

A

Ritonavir is a low potency protease inhibitor, but a very potent P450 inhibitor

Boost concentrations of other drugs metabolized by CYP450 enzymes

39
Q

Integrase inhibitors

A

-tegravir

Inhibit HIV integrase enzyme

Systemic Tx of HIV-1 and 2

Bictegravir

Cabotegravir

Dolutegravir

Elvitegravir

Raltegravir

40
Q

Side-effects of INSTIs in HIV Tx

A

Weight gain and Tx emergent obesity

Elevated creatinine kinase

Muscle pain

41
Q

Enfuvirtide (T20)

A

Fusion inhibitor that binds to HIV-1 gp41 fusion proteins

Only used in Pts not responding to other ART medications

Not effective against HIV-2

42
Q

Maraviroc

A

HIV entry inhibitor

CCR5 antagonist that prevents binding of R5 tropic HIV-1 strains to the CCR5 co-receptor

Thus CCR5 tropic-HIV envelope/host cell fusion is inhibited

HIV co-receptor tropism testing should be performed before using maraviroc

43
Q

Side-effects of Maraviroc

A

Liver damage that mimics allergic reactions

CV events

Postural hypotension

Increased risk of infection/malignancy

44
Q

ART

A

Typically combo of two NRTIs + 1 NNRTI or +1 INSTI

45
Q

Pre-exposure prophylaxis (PrEP) for HIV

A

Tenofovir (TDF) + emtricitabine (FTC)

Extended-relase formulation of cabotegravir (INSTI drug) given IM injection every two months

PrEP candidates must be screened for HIV infection before Rx and every three months thereafter

46
Q

What test is used to ID anti-retroviral drug resistance

A

RT-PCR

and gene sequencing of drug resistance genes

47
Q

Immune reconstitution inflammatory syndrome (IRIS)

A

Caused by renewal of immune response against preexisting oppurutnistic pathogen infections following initiation of ART in an HIV-infected Pt

Tx for common OI pathogens (i.e. Pneumocytsitis or Mycobacteria) should be initiaed before or along w/ ART if possible (using Bactrim for PCP)

Bactrim prophylaxis should be used in those w/ hyper IgM syndrome and SCID

48
Q

Human T lymphotrophic viruse type I (HTLV-1) is tropic for?

A

HTLV-1 is tropic for CD4+/FoxP3+ TREG lymphocytes

49
Q

Infections of what population is HTLV-1 most prevalent?

A

Persons of African ancestry

50
Q

HTLV-1 latency period

A

Typically between 10-30 years between initial infection and onset of disease

51
Q

What malignancies are associated w/ HTLV-1 infection?

A

Adult T cell leukemia/lymphoma

ATLL is often aggressive and refractor to chemotherapy - death w/i 12 mo.

52
Q

When do HIV+ Pt’s have highest viral load (untreated)

A

During the acute retroviral phase and when the disease progresses to AIDs

53
Q

HTLV-1 infection is associated with what metastatic disease?

A

Adult T cell leukemia

54
Q

A patient is POSITIVE in the HIV p24 antigen/antibody ELISA test, NEGATIVE in the HIV-1/HIV-2 discrimination ELISA, and POSITIVE in the HIV RT-PCR test (NAATs). What is the MOST LIKELY conclusion?

A

Pt has been infected for a very short period of time

55
Q

An untreated patient has been HIV-infected for 12 years. Their CD4 count remains in the normal range, their viral load is low, they have no symptoms, and they have had no infections with opportunistic microorganisms.

What host genetic factor explains this unusual disease progression?

A

Host carries one copy of the CCR5△32 mutation (long-term non-progressor)

Two copies - host would not become infected

56
Q

In which stage of a typical, untreated HIV infection is the virus disseminated to the central nervous system and lymphoid tissues throughout the body?

A

During the acute retroviral syndrome

57
Q
A

E. The HIV integrase enzyme integrates the viral RNA genome (integrase incorporates proviral DNA into host genome)

58
Q

What test is used to determine HIV infection in neonate?

A

RT-PCR

If mother is HIV+, maternal IgG will be present in neonate (that and HIV in neonate will suppress ability for endogenous IgG production)

59
Q
A

D. Abacavir is a nucleoside analogue that inhibits the HIV reverse transcriptase enyzme

60
Q

Maraviroc

A

Binds and antagonizes CCR5 receptor on host cell, preventing co-receptor binding of HIV

61
Q

Integrase enzyme inhibitor suffix

62
Q
63
Q

Example of CCR5 antagonist

64
Q

Host is heterozygous for CCR5△32 in context of HIV

A

Long-term non-progressor

65
Q

Host is homozygous for CCR5△32 in context of HIV

A

HIV resistant individuals - remain uninfected despite long-term HIV exposure

66
Q
A

D. Uninfected despite exposure

67
Q
A

B. (AIDS = CD4+ T cell count less than 200 cells/ul)

68
Q
A

C. Keep Pt on same ART, periodically perofrming plasma viral load testing and CD4+ T cell count

Only test for antiviral drug resistance with Tx failure

69
Q

Does maraviroc Tx HIV-1 or 2?

A

HIV-1

Has not been tested against HIV-2, and is only used to Tx HIV-1

70
Q

Do non-nuceloside analogue reverse transcriptase inhibitor (NNRTI’s) Tx HIV-1 or 2?

A

HIV-1

NNRTI’s do no work against HIV-2

71
Q
A

D and E

Bactrim is used to Tx prophylactically for Pneumocystis jiroveci

MI Immuno/Heme (35 decks)

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