Infectious Disease Unit 2 > Human Retroviruses > Flashcards

Human Retroviruses Flashcards

(18 cards)

Study These Flashcards
1
Q

2 unique characteristics of retrovirus lifestyle

A

In lab: Reverse transcription and integration into host chromosome

In clinic: associated with serious human disease

  • Immune disorders (AIDS)
  • Cancers (leukemia/lymphoma)
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2
Q

Retrovirus structure/proteins

A

Structural Proteins:

1) Envelope (gp120, gp 41): derived from host cytoplasmic membrane; determine host range of retroviruses (usually highly specific with respect to host/tissue types)
2) matrix (p17)- between core and envelope
3) capsid: Gag proteins (group associated antigens); p24–may contain protease

4)Viral enzymes: reverse transcriptase, protease (sometimes integrase, ribonuclease H - RNase)

Viral genome: 2 RNA molecules

Lipid bilayer

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3
Q

Life cycle steps of retroviruses

A
  • Binding to receptor/Entry
  • Reverse transcription in cytoplasm–acquire LTR - enter nucleus
  • Genome integration (establish persistent infection)
  • Viral gene transcription by host RNA polymerase
  • viral mRNA made by host RNA polymerase & processed; unspliced RNAs encode Gag/Pol
  • virus release via budding from membrane
  • virus maturation–protease cleaves individual proteins
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4
Q

Life cycle steps targeted by anti-retroviral drugs

A
  • Entry inhibitors
  • RT inhibitors
  • Integrase inhibitors
  • Protease inhibitors
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5
Q

What cancers are HIV patients getting and why is this important

A

AIDS-defining:

  • Kaposi Sarcoma
  • Non-Hodgkin’s Lymphoma
  • Cervical cancer

Non AIDS-defining:

  • Anal Cancer
  • Hodgkin’s lymphoma
  • Liver cancer
  • skin cancer
  • head and neck cancer
  • lung cancer
  • kidney cancer

More HIV-infected individuals are dying of HIV-associated cancer. They are more aggressive and progress faster. Lately we have seen decreases in AIDS-related cancers with HAART, but not for Non-AIDS related cancers, perhaps even increase)

  • Develops younger
  • progresses faster to invasive cancer
  • atypical pathology/high tumor grade
  • more aggressive/poorer outcomes
  • higher relapse rate
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6
Q

Potential Contributing factors to HIV pts developing cancer

A
  • Virus co-infections: HPV, HBV, HCV, HHV-8, EBV
  • Behavior risk factors (smoking)
  • Direct effects of HIV (proto-oncogene transactivation, inhibit p53, endothelial abnormalities by HIV, including proangiogenesis)
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7
Q

What are different in treatment for these cancers

A

The chemo and antiretroviral drugs can interact and/or have overlapping toxicities.

Chemo agents are often degraded by CYP450 enzymes in liver. Many antiretroviral drugs can inhibit or enhance CYP450 enzymes, altering concentrations of chemotherapy drugs.

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8
Q

What is HTLV

A

Human T-cell Lymphotropic Virus

-delta-retrovirus that infects human T lymphocytes and causes lymphoproliferative disorders

  • HTLV-1 = first retrovirus linked to human disease
  • HTLV-2 = closely related to HTLV1 but aren’t sure of related diseases
  • HTLV-III, HTLV-IV (HIV-2) –don’t know much about
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9
Q

HTLV epidemiology and transmission

A
  • Southern Japan, Caribbean countries, South America, Africa
  • isolated pockets in Iran
  • about 20 million infected globally

Suggested transmission (not 100% sure)

  • Mom to child via breastfeeding
  • sex
  • exposure to infected blood products
  • sharing needles/syringes
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10
Q

Human disease caused by HTLV-1

A
  • Adult T cell leukemia/lymphoma
  • HTLV-I- associated myelopathy (HAM)–tropical spastic paraparesis
  • Uveitis

Others needing further study (arthritis, pneumonitis, urinary tract disorders, increased susceptibility to infectious dz)

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11
Q

What is ATL/Types of ATL

A
  • lymphoproliferative disorder; enlarged lymph nodes, skin lesions, lytic bone lesions and hypercalcemia–hard to treat and poor prognosis
  • tumor derived from single transformed cell infected by virus
  • Viral Tax protein implicated in initiating events ultimately leading to lymphoma

4 types:

1) Acute ATL (60%)- median survival 6 mo
2) Lymphomatous ATL (~20%)- similar to acute but few circulating abnormal cells
3) Chronic ATL: median survival 2 years
4) Smoldering ATL (less than 5% of pts; median survival over 5 years)

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12
Q

What factors influence whether HTLV-I infection will induce ATL or HAM

A
  • Think it is based on immune response—develop stronger immune response leads towards HAM vs immune suppression leading towards ATL
viral strains
virus infection route
other host immune regulations
particular MHC haplotypes
viral load
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13
Q

Adult T cell Leukemia/Lymphoma (ATL)

A

First reported in Japan

  • only small fraction of infected subjects develop ATV
  • Geographic correspondence between HTLV-1 and ATL
  • oncogenic capacity of HTLV-1 in animal models
  • HTLV-1 cultivated from ATL cells
  • clonally integrated HTLV in provirus in leukemic cells
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14
Q

ATL Disease Progression

A

HTLV-I infection

  • Clonal proliferation by HTLV-I tax /Immune invasion
  • Malignant expansion (produce really messed up chromosomes in T cells)–alteration of host genoma
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15
Q

ATL treatment

A
  • allogenic hematopoietic cell transplantation
  • Multi-agent regimens
  • Antiviral therapy
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16
Q

HTLV-I Associated Myelopathy (HAM)

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A
  • also called tropical spastic paraparesis
  • resembles MS: weakness/stiffness of legs (1.3 bedridden in 10 years)
  • Higher HTLV-I replication and stronger immune response than ATL (activates cytokines/chemokines)
  • possibly autoimmune destruction of neural cells by T cells
17
Q

retroviral genome structure

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A
  • carry 2 copies of RNA genome
  • typical retrovirus has 3 essential genes: gag, pol, env
  • Gag gives rise to matrix protein (MA), capsid protein (CA) and nucleic acid-binding proteins (NC)
  • Pol= protease + reverse transcriptase (HIV pol also carries integrase (IN))
  • Env region: encodes surface protein (SU) and small transmembrane protein (TM)
  • LTR = long term repeats; repeated segments of DNA at either end of retrotransposon/proviral DNA. Formed by reverse transcription of retroviral RNA and contain transcription regulators. Used by viruses to insert genetic material into host genomes
    Complex retroviruses also have other accessory genes products
18
Q

Major classes of retroviruses

Study These Flashcards
A

Acute transforming: uncommon in nature; defective replication, requires helper virus

Non-acute transforming: common in nature; competent replication

Transacting: Uncommon in nature; HTLV-1, BLV; competent replication

Infectious Disease Unit 2
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