1
Structural Virology
Lecture 8
Pavel Plevka
2
Retroviridae
3
Reverse transcriptases
Murine leukemia virus (MLV)
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
4
5
Reverse transcriptase
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
6
7
Retrovirus RNA and DNA forms of genome
8
Reverse transcription
of retrovirus genome
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
9
Genomes inside virion
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
10
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
11
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
12
13
14
Virion and genome organization
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
15
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
16
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
17
Kissing RNA
loops
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
18
The HIV trans-activation response (TAR) element is an RNA element which is known
to be required for the trans-activation of the viral promoter and for virus
replication. The TAR hairpin is a dynamic structure[1] that acts as a binding site for
the Tat protein, and this interaction stimulates the activity of the long terminal
repeat promoter.[2]
Further analysis has shown that TAR is a pre-microRNA that produces mature
microRNAs from both strands of the TAR stem-loop.[3] These miRNAs are thought
to prevent infected cells from undergoing apoptosis by downregulating the genes
ERCC1 and IER3.[4]
19
Retrovirus transcription start and terminator?
20
Retrovirus transcription
21
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
22
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
23
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
24
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
25
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
26
SRC
27
28
29
30
31
32
Early transcription
33
Functions of Tat and Rev
Tat – translation of whole genome
Rev – transport of mRNAs to cytoplasm
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
34
35
36
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
37
38
Virion assembly
39
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
40
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
41
HIV infection - AIDS
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
42
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
43
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
44
Learning outcomes
• describe the retrovirus virion
• describe the main features of the retrovirus
genome
• explain the main features of the retrovirus
replication cycle
• give examples of retroviruses and explain their
importance
• discuss endogenous retroviruses
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
45
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
46
Learning outcomes
• explain the importance of HIV
• describe, with the aid of a labelled diagram, the HIV-1
virion
• describe the HIV-1 genome
• write an illustrated account of the replication cycle of
HIV-1
• discuss the variability of HIV-1
• discuss the effects of HIV infection on the host
• evaluate approaches to the prevention of HIV
transmission
47
Hepadnaviruses and other reverse transcribing DNA viruses
48
World distribution of Hepatitis B
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
49
Hepatitis B virion structure
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
50
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
51
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
52
HBV transcripts
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
53
Hepatitis B genome organization
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
54
HBV S, M, L proteins
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
55
56
57
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
58
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
59
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
60
61
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
62
• explain the importance of HBV
• describe the HBV virion and non-infectious
particles
• outline the main features of the HBV genome
• describe the HBV replication cycle
• evaluate means of preventing and treating HBV
infection
Learning outcomes
© 2012 John Wiley & Sons Ltd.
www.wiley.com/college/carter
63