Human Immunodeficiency Virus

Dsme Joyce Pohan ,dr M

Biomed

Genus Retroviridae
Lentivirus, which literally means
slow virus
This virus attacks the immune system

There are two strains HIV 1 & HIV 2

 It belongs to a group of retroviruses.

These contain RNA, the genetic material
material of HIV
The outer layer of the HIV virus cell is covered
in coat proteins, which can bind to certain
WBCs. This allows the virus to enterthe cell,
where it alters the DNA.
The virus infects and destroys the CD4
lymphocytes which are critical to the bodys
immune response

History of HIV
History
of
HIV
The HIV virus first came to light during the
early 1980s.
A number of healthy gay men in New York
began to develop rare opportunistic
infections& cancers, that were resistant to
treatment.& cancers, that were resistant to
treatmen
One such viral opportunistic infection is
cytomegalovirus that causes blindness
&inflammation of the coloninflammation of
the colon

In The Beginning...
1675 - Speculation that HIV was
?
first
transmitted from
chimpanzees to
humans
1926-1946 - Scientists believe HIV
first
spread from monkeys to
humans
1959 - First proven AIDS death
1978 - Gay men in US and Sweden
begin showing signs of what
is now known as AIDS

Structure of
HIV

Human Immunodeficiency Virus

An RNA retrovirus subfamily Lentivirus
Contains:
2 copies of RNA
Enzymes:

Reverse Transcriptase
Integrase
Protease

Two major envelope proteins:

gp120
gp41

Antigen p24 adalah core antigen virus HIV

petanda adanya infeksi HIV-1, ditemukan beberapa
hari-minggu sebelum terjadi serokonversi sintesis
antibody terhadap HIV-1.

Antigen gp120 adalah glikoprotein permukaan HIV-1

yang mengikat reseptor CD4+ pada sel T dan
makrofag.

Usaha sintesis reseptor CD4+ untuk mencegah

antigen gp120 menginfeksi sel CD4+.

Gen envelop sering bermutasi menyebabkan jumlah

CD4 perifer menurun, fungsi sel T yang terganggu,
aktifasi poliklonal sel B hipergamaglobulinemia,
antibody dapat menetralkan antigen gp120 dan gp41
tidak mencegah progress penyakit oleh karena kecepatan
mutasi virus yang tinggi.
Protein envelop menyandi gp120, memproduksi
antibody yang efektif dan produktif oleh pejamu.

 The genome of HIV is encoded on two identical

strands of RNA when the virus is in the freeform.
It has nine open reading frames (leading to
nineprimary translation products) but 15
proteinsare actually made in all as a result of
cleavage of three of the primary products.
The GAG gene and the GAG and POL
genestogether are translated into polyproteins
whichare then cleaved by a protease.

GAG polyprotein is cleaved to into

four proteins
matrix protein (p17) which anchors the
gp160receptorreceptor
capsid protein (p24) which forms a capsule around the
RNA genome
the nucleocapsid protein which binds to the HIV
packaging signal on viral
p6 which plays a role in incorporating proteins into
new virons.
ENV gene is translated to gp160 which is then cleaved by
a host cell protease found in the Golgi body to:
Gp41
Gp120
Together these form the HIV receptor

POL polyprotein is
cleaved to
Protease
Reverse transcriptase
Integrase

Three of these are incorporated into the virus:

Tat and Rev are regulatory proteins

Vpu (HIV-1) indirectly assists in assembly

The HIV receptor

Gp160 is composed of gp41 and gp120 and forms the

receptor for binding to the host cell (CD4positive cells).
The gp41 portion is half embedded in the membrane
envelope and interacts with gp120 portion on the
exterior side of the membrane
Each receptor is composed of 3 subunits of gp41and 3
subunits of gp120.

es.monocytes.
Life cycle of HIV

HIV particles enter the body in a fluid as it can not survive

without
a support
The virus
targetsmedium.
any cell expressing CD4, including T helper
cells, macrophages, monocytes dendritic cells and
monocytes

Human Immunodeficiency Virus

Lifecycle in Host Cell

Life Cycle of HIV virus

1.

Interaction between viral envelope proteins and

CD4 receptor and co-receptors leads to binding
of the viral envelope and host cytoplasmic
membrane
2. Viral reverse transcriptase catalyses the
conversion of viral RNA into DNA
3. Proviral DNA enters the nucleus and becomes
integrated into chromosomal DNA of host cell
(catalyzed by integrase)
4. Expression of viral genes leads to production of
viral RNA and proteins.
5. Protease enzyme cleaves proteins into
functional mature products.
6. Viral proteins and viral RNA are assembled at
the cell surface into the new viral particles and

Human Immunodeficiency Virus

Life Cycle in Host Cell
HIV tends to infect CD4+ T Cells, because
CD4 receptor has high affinity for gp120
(HIV viral-envelope protein)
CD4+ T Cells initially die in acute phase
due to cytopathologic damage by virus.
CD4+ T Cells then chronically die from:

Chronic activation of T cells

Inhibition of thymic output of T cells
Suppression of the bone marrow
Destruction of lymph-node architecture
Low-level ongoing infection of memory CD4+ T
cells

Replikasi
HIV

espon Imun terhadap Infeksi Virus HIV

Normal Immune Response

T-cells make
antibodies

Virus binds to T-cells

Virus

Antibodies
bind to
virus

Tcells

Normal response: Virus invades blood

stream and binds to lymphocytes.
Lymphocytes make antibodies to the
virus. Antibodies bind to the virus and
destroy
the virus.

Viru
s

Antibodies
kill virus

Immune Response to HIV

HIV

HIV destroys Tcells (CD4 cells)

T-cells cannot
produce antibodies
Cannot destroy virus

Respon Imun terhadap Infeksi Virus HIV

Sesaat setelah infeksi virus HIV, viral load

(kadar virus) individu yang terinfeksi akan
mengalami pertumbuhan secara ekponensial
Respon imun terhadap HIV melibatkan antibody
maupun sel T mampu mengontrol jumlah
virus HIV, tetapi tidak mengeliminasinya
setelah infeksi antigen p24 di dalam serum

Sel T CD8+ (Sitotoksik)

berubah menjadi sel CTL --> Kerja CTL cara induksi apoptosis
CTL menghambat replikasi virus dan berperan penting dalam
kontrol awal infeksi HIV
Sifat kualitatif respon sel T CD8+ oleh setiap individu
ditentukan oleh tipe MHC yang dimilikinya
Sel T CD8+ (Non Sitotoksik)
CD8 anti viral factor (CAF)
mengendalikan replikasi virus pada sel CD4+ yang
terinfeksi
menghambat masuknya virus, dengan
mengganggu pengikatan gp120 ke HIV-coreceptor
CCR5
Aktifitas CAF tertinggi terjadi pada saat awal
proses penyakit.

Sel T CD4+

infeksi HIV, bersamaan dengan Sel T

CD8+ mengaktifkan respon Sel T
helper (Th) CD4+,
Sel T CD4+ spesifik terhadap HIV
terdeteksi di awal munculnya penyakit

 Antibodi
Envelope HIV adalah target utama respon imun
humoral,

antibodi netralisasi mentargetkan epitop protein

envelope.

Virus menghindari efek antibodi netralisasi.

Beberapa epitop netralisasi bersifat cryptic,
Antibodi harus memiliki afinitas yang kuat dan cepat
sehingga dapat berkompetisi dengan ligand alaminya.
Virus juga bisa melindungi epitop netralisasi utama
dengan protein glikan
Cara penghindaran lain adalah sifat glikoprotein yang
mudah bermutasi yang membuat virus terhindar dari
antibodi netralisasi (translated by undil).

T-Cell Count
If 1,200 or higher, the individual has a
normal immune system.
If 800 or less, the immune system is
weakened and individual is susceptible to
infection.
If 200 or less, AIDS is diagnosed.
Once a person is diagnosed with AIDS, she
or he is always categorized as having
AIDS, even if her or his T-cell count
increases.

Criteria for Diagnosing AIDS

A CD4 cell (type of T-cell) count of

200
or less,
or
One opportunistic infection.
An opportunistic infection is an
infection
that typically does not affect
individuals with
normal immune systems.

Effects of HIV on the immune system 3

areas:
1. Destruction of CD4+ T cells
population
2. Immune effects due to HIV infection
to AIDS
3. Progression of HIV infection to AIDS

Transmission
HIV is transmitted from person to person in
severalHIV is transmitted from person to person
in severalways:ways:
Through unprotected sex with an infected
personThrough unprotected sex with an infected
person
Exposure to infected bloodExposure to infected
blood
By the use of contaminated equipment for
injectionsBy the use of contaminated equipment
for injections(by drug users or medical
treatment in developing(by drug users or
medical treatment in
developingcountries)countries)
From an infected mother to her baby before
orFrom an infected mother to her baby before
orduring birth, or by breast feedingduring birth,
or by breast feedin

Diagnosis of HIV

HIV antibody ELISA if positive, is always followed by a

confirmatory Western Blot
Rapid HIV antibody test
Sensitivity and Specificity 99%!
Results in 5 to 40 minutes usually
Used in:

Occupational Exposure
Pregnant women presenting in labor with no previous HIV testing
Patients who are unlikely to return for results of HIV test

HIV viral load

First choice for diagnosing possible acute HIV

HIV p24 Antigen

Is the first antigen to be elevated in acute HIV

Can be used for diagnosis of primary (acute) HIV