Human Immunodefiency Virus Type 1 Lentivirus

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Human Immunodefiency Virus Type 1Lentivirus
Virion
Genome
Genes and proteins
Viruses and hosts
Diseases
Distinctive characteristics
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Human Immunodefiency Virus Type 1Lentivirus

• Virion
• Spherical enveloped particle.
• Diameter 100 nm.
• Conical capsid.

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Human Immunodefiency Virus Type 1Lentivirus

• Genome
• Linear ss RNA, positive sense.
• Two identical segments, each 9.3 Kb.
• Cellular tRNAlys3 molecules packaged in virions
  used as primers for reverse transcription.

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Human Immunodefiency Virus Type 1Lentivirus

• Genes and proteins
• Four capsid proteins MA, CA, NC,p6
• Three enzymes PR, RT, IN
• Two envelop proteins SU, TM
• Six regulatory proteins Vif, Vpu, Vpr, Tat,
  Rev, Nef

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Human Immunodefiency Virus Type 1Lentivirus

• Viruses and hosts
• Human immunodeficiency virus types 1 and 2
  (HIV-1, HIV-2).
• Simian immunodeficiency virus.
• Equine, bovine, feline immunodeficiency viruses.

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Human Immunodefiency Virus Type 1Lentivirus

• Diseases
• Acquired immune deficiency syndrome (AIDS) first
  described in 1981.
• A major global pandemic today (more than 30
  million people infected).
• HIV replicates in and kills lymphocytes and
  macrophages.
• Results in depletion of CD4 T cells to render
  host immune-incompetent.
• As a result, opportunistic infections by other
  pathogens are often fatal.
• HIV is transmitted through sexual contact and
  blood exchange.

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Human Immunodefiency Virus Type 1Lentivirus

• Distinctive characteristics
• Proviral DNA can enter nucleus without
  requirement for cell division.
• Lentiviruses make a complex set of singly and
  doubly spliced mRNAs.
• Six regulatory proteins control virus production
  and pathogenesis.

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Virion

• Human immunodeficiency virus type 1 (HIV-1) and
  acquired immunodeficiency syndrome

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Virion

• HIV-1 infection leads to a progressive loss of
  cellular immunity and increased susceptibility to
  opportunistic infections

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Virion
Fig. 26.2 Diagram of structure of HIV-1 virion.
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Genome

• HIV-1 is a complex retrovirus

Fig. 26.3 Genome structure and RNA splicing
pattern of HIV-1.
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Genes and proteins

• HIV-1 is a complex retrovirus

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Genes and proteins

• HIV-1 is a complex retrovirus

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Genes and proteins

• HIV-1 targets cells of the immune system by
  recognizing CD4 antigen and chemokine receptors

1. gp120 on the virion binds to CD4 on the cell
   surface
2. gp120 undergoes a conformational change that
   exposes regions that bind to chemokine receptors
   (CCR5 or CXCR4)
3. The close proximity of the viral and cellular
   membranes results in their fusion

Fig. 26.4 Model of HIV-1 entry.
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Genes and proteins

• Virus mutants arise rapidly because of errors
  generated during reverse transcription
• Unlike other retroviruses, HIV-1 directs
  transport of proviral DNA into the cell nucleus
• MA and Vpr facilitate nuclear transport
• Can infect cells that are not actively dividing
• Latent infection complicates the elimination of
  HIV-1
• 1 in 100 infected cells actively express viral
  RNA
• Cannot be readily distinguished from uninfected
  cells by immune system

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Genes and proteins

• The Tat protein increases HIV-1 transcription by
  stimulating elongation by RNA polymerase II

(a) In the absence of Tat, RNA polymerase II
molecules that initiate transcription at the
HIV-1 promoter lack processivity and most are
released (b) Tat recruits cyclin T and
cyclin-dependent kinase-9 (Cdk9) to the
transcription complex shortly after
initiation (C) Hyperphosphorylation of C-terminal
domain (CTD) of RNA polymerase increases
processivity
Fig. 26.5 Mechanism of Tat function.
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Genes and proteins

• The Rev protein mediates cytoplasmic transport of
  viral mRNAs that code for HIV-1 structural
  protein
• CRS
• RRE

Fig. 26.6 Mechanism of Rev function.
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Genes and proteins

• Together, the Tat and Rev proteins strongly
  upregulate viral protein expression
• The Vif protein increases virion infectivity by
  counteracting a cellular deoxycytidine deaminase
• The Vpr protein enables the preintegration
  complex to be transported to the nucleus

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Genes and proteins

• The Vpu protein enhances release of progeny
  virions from infected cells
• Degradation of CD4.
• Enhancement of virus release from the plasma
  membrane.
• The Nef protein is an important mediator of
  pathogenesis
• Decrease in the surface expression of CD4 and MHC
  1.
• Enhancement of virus infectivity.
• May induce phosphorylation of matrix protein,
  which could increase virus infectivity

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Genes and proteins
(a) In the absence of Vpu, CD4 interacts with
gp160 in the endoplasmic reticulum, Vpu binds to
the cytoplasmic domain of CD4 and through
interaction with TrCP directs CD4 to the
proteasome degradation pathway. (b) Nef binds to
the cytoplasmic tail of CD4 at the inner surface
of the plasma membrane, and via interaction with
AP-2 increases uptake of CD4 into clathrin-coated
pits
Fig. 26.7 Down-regulation of CD4 expression.
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(No Transcript)
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Key Terms

• Major histocompatibility complex (MHC) protein
• Myristate
• NF-kB (nuclear factor-kB)
• Opportunistic infections
• Preintegration complex
• Proteasomes
• Src-related kinases
• T-cell receptor
• Transgene
• Ubiquitination

• Azidothymidine
• CD4 antigen
• CD4-positive T lymphocytes
• Chemokines
• Cytokines
• Cytotoxic T lymphocytes
• Dendritic cells
• Epitopes
• Importin
• Latent infection
• Macrophage