RETROVIRUSES

DR GEORGINA ODAIBO
DEPARTMENT OF VIROLOGY
COLLEGE OF MEDICINE
UNIVERSITY OF IBADAN
 VIRUSES
 ------- known ------- organisms

 Reproduce by -----------

 Genetic material either ----- or ------

 Several ------ of Viruses

 Have affinity for ------

 Retroviruses

 They are a group of ------ viruses with a unique -----

system.
 They posses an enzyme --------which is used to reverse
transcribe the ------ to ----- within the ----- cell.

 The mechanism by which the human retroviruses

cause disease involve an intimate relationship with --
--- and hence their medical importance
 VIRUS CLASSIFICATION
 "previous" classification into subfamilies (-----
, -----, -----) is no longer appropriate, since the
genera that made up, for example,
oncovirinae are no more ----- (or similar) to
one another than they are to members of
other previously designed subfamilies.
Retroviruses are currently classified into ------
 NEW CLASSIFICATION
 Genus ------
 ------ virus
 Genus -------
 Subgenus: -------virus group
 ------ retrovirus
 Subgenus: ------ virus group
 -------- virus
 ---------- virus
 Genus ------
 ------ virus
 Genus ------- group
 -------- virus
 Genus ---------
 ------ virus
 -------- virus (HTLV)
 Causes -------
 ------ tumour of ----- cells which infiltrates ---- and ---- (Less than ----of HTLV
1 infected individuals develop this malignancy)
 CLASSIFICATION CONT.
 Genus ------
 Subgenus: ------ group
 ------ virus
 Subgenus: ------ group
 ----- virus
 Subgenus: ------ group
 ----- virus ----
 Subgenus: ------ group
 ------ virus
 ------- virus
 Subgenus: ------ group
 ------- virus 1
 ------ virus 2
 ----- virus
 ------ virus
 Genus ----
 ------- virus
 MORPHOLOGY
 ----- are enveloped; slightly ------; shape is ----;
----- in diameter.
 Surface projections of envelope is ---- (surface
appears ----), or distinct (----nm long -----);
bears ----; dispersed evenly over -----.
 ----- is isometric (to -----), or -----shaped (or a ----
- cone).
 ---- only of one kind.
 Genome:
 Genome is -------.
 ----- stranded.
 Direction: -----; genomic nucleic acid is -----
sense.
 ----- dimeric (monomers held together by --
---- ).
 Total genome of one monomer ---- - -----
nucleotides long. 5' terminus has a ------.
 Host

 Virus infects -------.

 VIRUS REPLICATION
 ------ contain viral RNA and several copies of ------ (DNA ----).
 After infecting a cell, the ------ is used to make the initial copies of
viral DNA from ------.
 Once a DNA strand has been synthesized, a ------ is made.
 These double strand copies of viral DNA are inserted into the host-
cell ----- with the help of another enzyme, -----, to form a pro-virus
 --------- is used to make virus-related RNA. These RNA strands serve
as templates for making new copies of ------and serve also as -----.
mRNA is translated into -------.
 New viral particles are assembled, bud from the -----, and are
released.
 ----- is acquired from the cell membrane as the mature virus buds
out
Virus Replication Cycle
 LABORATORY DIAGNOSIS
 Serology
------ ELISA

 Direct detection of virus

---- ELISA
Culture from ----
----
 Treatment

 ----- drugs are medications for the treatment of

infection by retroviruses, primarily ----.
 Different classes of antiretroviral drugs act at -----of
the HIV replication cycle.
 ----- Inhibitor
 ----- Inhibitor
 ----- Inhibitor
 ----- Inhibitor
 ------- is known as -------(HAART).
Human Immunodeficiency Virus
 Belongs to the Family -----
‘Retro’ -----
RNA DNA (usual flow is ---- - -----)
 Genus -----
 Involvement of ---- system
 Clinical ----
 Weak ---- response
 AIDS
 Acquired Immunodeficiency Syndrome
 Caused by -----
 Mature retrovirus particles are ----- in
shape with a diameter of ------

 Consist of 3 major genes

 -----  P-----, P-----, P----
 -----  gp----, gp---- (gp----)
 -----  enzymes – ----, ----, ----

 Other 6 minor genes

 ----, ---, ---,----------, ------, -----
STRUCTURE OF MATURE HIV
 STRUCTURE OF HIV GENOME

vif vpr rev vpu tat nef

GAG POL ENV

LTR tat rev LTR

P17 P6 P10 P32 Gp120 Gp41

P24 P9 P66/51

Core proteins Viral enzymes Envelope proteins

 TRANSMISSION
THREE MAJOR MODES
1. ------
* -----sexual
* ----sexual

Influenced by:
- -----
- -------
- --------
2. ---- to -----
- During ---
- During ---
- During ----

3. Contaminated ---- and -----

 Blood ------
 Use of ---- needle and syringes
 other sharp objects/sharing/contaminated
 CELLULAR RECEPTORS
 ----- Molecules
 ----- co-receptor
 ----
 Associated with entry of ------
 ----- isolates
 -X---
 ---
 --- tropic
 Non ---- isolates
 -R---
 ----- (--- tropic)
 Individuals with ----- are largely resistant to infection with HIV-1
heterozygosity for the mutation associated with ------
Critical role of T4 Lymphocyte in the Human
Immune Response
SECRETTION OF GROWTH
AND DIFFERENTIATION
FACTORS FOR LYM[PHOID ACTIVATION OF
CELLS MACROPHAGES

INDUCTION OF
CYTOTOXIC T-
CELL FUNCTION

INDUCTION OF
SECRETION OF NATURAL
HAEMATOPOETIC T4
KJLLER (NK)
LYMPHOCYTE
COLONY AND CELL FINCTION
STIMULATING
FACTORS

SECRETION OF FACTORS
WHICH INDUCE NON-
LYMPHOID CELL INDUCTION OF
FUNCTION SUPPRESSOR CELL
FUNCTION

INDUCTION OF B CELL
FUNCTION
 HOW HIV CAUSES AIDS
 HIV infects and destroys --------
 ------ cells
 Destruction of these cells lead to ------
 Opportunistic infections sets in
 ------ infections (TB, )
 ----- complications (diarrhea)
 ------ Infections (Rashes, KS)
 ----- loss
 Hence AIDS
 HETEROGENEITY OF HIV
 Most striking feature of HIV is its --------
 ------ virus particles are generated each day with ----- at
each round of replication

 ---- error-prone (Mutation rate ----- – ------ bp

substitution)

 HIV-1 mutates one ------ per ----

 Recombination of retroviruses
 Occurs at a rate of 2% ----- per ------
 Contributes to ----- among virus ----
  ----- pressure
 Host ----- response
 Cell -----
 Host ---- make-up

 Variation occurs in
 An individual at ------
 Among individuals in -----
 Among individuals in ------ region

 HIV has been classified based on -----

 PHENOTYPIC VARIATION
Variation in biological xtic of isolates
 ----- inducing/----- inducing
 ----/---- replicating
 -------/------

Virulence
 HIV TYPES AND SUBTYPES
TWO TYPES OF HIV
------ and -------
 SIMILARITIES
 Both associated with -----
 -----
 Tendency to cause ------
 Ability to -----
 DIFFERENCES BETWEEN HIV-1 AND HIV-2

 Differ by ----% in ------

 Major difference in ------
 ------- by both viruses is possible
 DIFFERENCES BETWEEN HIV-1 AND HIV-2
CHARACTERISTICS HIV-2 VERSUS HIV-1
Mode of transmission -----
Likelihood of perinatal 0.4% - 1.2% per birth for HIV-----
transmission from mother versus 25 – 35% per birth per
to child HIV-----
Likelihood of sexual Approximately 3 fold reduced for
transmission per sexual HIV------
exposure
Rate of development of <0.5% per year for HIV----- versus
AIDS 3 - 5% per year for HIV-----in
some cohort
Rate of development of Approximately 1% per year for
abnormal CD4+ HIV----- versus 10% for HIV----
lymphocytes -

Distribution is Worldwide
Distribution limited to West Africa
NB: HIV---- is more virulent than HIV---
-
 HIV SUBTYPES
 Classification is based on --------
HIV-1
Three groups
 Group ---- (----)
 Group ---- (----, ---- or ----)
 Group ----(----)
Group M

9 ------------------- 16---
(--- - ---, --- - ---, --- - ---) e.g. ----- (---
-)
 CRF01_AE Reference strain: CM240 Subtypes: A, E

CRF02_AG Reference strain: IbNG Subtypes: A, G

HIV-2
 ---- Subtypes
----- – ----

Implication of variability
 ----
 -----
 -----
 HIV TESTING
DIAGNOSIS OF HIV INFECTION
Mainly by ---------
Serologic Techniques
 Screening
 --------- (-----)
 ---- generation
 ---- generation
 ---- generation
 ---- generation
 ---- tests
 -----
 ----blot/---- Assays
Outcome of screening test
 ----- or ---- (NOT ---- or ----)
 Confirmatory Test
 Detection of ----- to ----
 ------ techniques
 Expensive
 ------ demanding
Results
 -----
 ------
 ------

Virus/viral antigen detection

 ----- detection ELISA
 ----- isolation
 Detection of ----- try -----
Diagnosis of HIV in newborns
 Problem with -------
 ---- detection assays
 ----

Monitoring progression of HIV infection and

therapy
 Progression to AIDS differs with ------ (slow ---- and
fast ----)

 Increase in HIV replication leads to increase in ------

and subsequently decrease in ------ cells
Viral Markers
 -----
 P----- -----
 Change from -----  ---

Cellular Markers
 ------- counts
 Extremely important for the ---- of HIV
infection
Virus and CD4 levels over the course of an
untreated HIV infection
SITUATION IN NIGERIA
 TRENDS OF HIV INFECTION
18
PREVALENCE (% ).
16
PREGNANT
14 WOMEN
12 STD
10
PTB
8
6
4
2
0

1
91

95
93

00
19

19

19

/2
00
20

YEARS
 HIV TYPES
 Circulation of HIV types 1 and 2

 Decreasing rate of HIV----

---- or problem of ---?
RATE OF HIV-1 AND HIV-2 INFECTION
AMONG POPULATION GROUPS
STD PATIENTS

16
PREVALENCE (%)

14
HIV-1
12
10 HIV-2

8
6
4
2
0
91 93 95 01
19 19 19 20
YEARS
Proportion of HIV-1 and HIV-2 infection in Nigeria
1999 National Survey 7%

4%
HIV-1
HIV-2
Mixed HIV
89%

2001 National Survey

1%

2%
HIV-1
HIV-2
Mixed HIV
98%
 CORRELATION OF DIFFERENT SUBTYPES AND
PHENOTYPIC CHARACTERISTICS OF HIV-1 ISOLATES
FROM NIGERIA
Phenotype No (%)
Subtypes Total
FR/SI FR/NSI SR/SI SR/NSI

A 10 (71.4) 1 (7.1) 2 (14.3) 1 (7.1) 14 (37.8)

B 1 (33.3) 1 (33.3) 1 (33.3) 0 3 (8.9)

C 7 (63.6) 2 (18.2) 1 (9.1) 1 (9.1) 11 (28.9)

E 2 (100.0) 0 0 0 2 (4.4)

A/C 1 (50) 0 1 (50) 0 2 (4.4)

NR 2 (50) 0 1 (25) 1 (25) 4 (15.6)

Total 23 (63.9) 4 (11.1) 6 (16.7) 3 (8.3) 36

FR  Fast replicating, SR  Slow replicating, SI  Syncytium

NSI  Non-syncytium inducing, NR  non-reactive
BASELINE HIV PREVALENCE AMONG SOME HIGH RISK AND BRIDGE
POPULATION GROUPS IN OYO STATE

Sub-pop. groups Location No Tested No (%) positive

High School (4) Saki 606 21 (3.5) {3-4.8}

Poly Students Saki 429 22 (4.9)

ITO Ibadan 164 6 (3.7)

APM Saki 212 10 (4.7)

BIT Saki 78 5 (6.4)

Ibadan 247 10(4.0)

AJP Saki 504 32 (6.3)

Ibadan 91 5 (5.5)
AMA Saki 383 40 (12.5)
Ibadan 283 20 (8.1)

RTW Saki 224 31 (13.8)

CSW Saki 61 29 (47.5)

Ibadan 243 52 (21.4)

Uniformed men Oyo 273 37 (13.6)

state

Fam. Uni.men Oyo 207 22 (10.6)

state

General Saki 574 38 (6.6)

Ibadan 413 21 (5.1)
 HIV SUBTYPES
 Isolation of a variant of HIV----- subtype -
---(HIV---- ---) from Nigeria in ----

 Identification of HIV-----subtypes --- from

Nigeria ----
Sequence analysis of HIV-1 IbNg and G
showed that both strains are ----
 Serological evidence of HIV----group ----.
mostly from S.E and N.E. parts of Nigeria

 Widespread distribution of HIV-----

subtypes ---, ----, ----and ----using --- assay
RECENT DATA FROM --- HIV SUBTYPING
PROJECT IN OYO STATE

 Partial sequencing of ---- and &--

regions

 Alignment with reference sequences

in the -----
 ---- based on concordance of both
regions
Viral Diversity in Oyo State
G
CRF02
URF
CRF06
Other

IBADAN SAKI
 THANK YOU
VERY MUCH
FOR LISTENING