SMK5401

MEDICAL MICROBIOLOGY

Prepared By:
Kalidasan A/L Vasodavan (GS40862)
BiomedSc (Hons.) MSU

Keshavardini A/P Sahathevan (GS39643)

BiomedSc (Hons.) MSU

DEPT. OF MEDICAL MICROBIOLOGY & PARASITOLOGY

FACULTY OF MEDICINE & HEALTH SCIENCES, UPM

Human Immunodeficiency Virus (HIV)

HIV: Derived from primate lentiviruses and a member of the retrovirus family,
etiologic agents of acquired immunodeficiency syndrome (AIDS).
Structure:
(a) Enveloped spherical virus
(b) Nucleocapsid with outer icosahedral
shell & inner cone shaped core
(c) Two identical copies of positive sense,
single stranded RNA genome
(d) Reverse transcriptase within capsid
(e) Lipoprotein envelope consist of lipid
from host cell membrane &
glycoprotein encoded by virus; outer
glycoprotein
knob
(gp120)
&
transmembrane portion (gp41)

Route of Transmission

Sexual
contact

Pregnancy,
Childbirth &
Breast feeding

Suitable host
on exposure

Injection
drug use

Occupational
exposure

Blood
transfusion,
Organ transplant

Virus tropism for

CD4-expressing
T
cells & cells of
macrophage lineage

HIV Replication Cycle

Step 1: Fusion of the HIV cell to
the host cell surface

Fusion is a merging of cell and virus

membranes that permits HIV proteins and
nucleic acids to enter the host cell.
Specific binding of the virus to CD4
receptor found on the surface of helper T
cells, regulatory T cells, monocytes, and
dendritic cells.
Coreceptor (CCR5 or CXCR4) on the
surface of lymphocytes or monocytes that
bind to the gp120 protein of HIV and
facilitate entry of viral nucleic acid and
proteins into the cell.

HIV Replication Cycle

Step 2: HIV RNA, reverse
transcriptase, integrase & other
viral proteins enter the cell

Preintegration complex (PIC) is composed

of viral RNA and proteins (nucleocapsid,
p6, Vpr, integrase, and matrix) as well as
some host proteins. It functions to reverse
transcribe genomic RNA into double
stranded DNA prior to integration into the
host genomic DNA.
Viral capsid that is internalized by fusion
is uncoated releasing the HIV genome and
all enzymes for replication within the
cytoplasm of the host cell.

HIV Replication Cycle

Step 3: Viral DNA is formed by
reverse
transcription
and
transported across the nucleus &
integrates into the host DNA.

Reverse transcriptase is an enzyme found

in HIV that creates double stranded DNA
using viral RNA as a template and host
tRNA as primers.
Integrase is an enzyme found in
retroviruses including HIV that permits the
viral DNA to be integrated into the DNA of
the infected cell forming a proviral DNA.
Production of new viral RNA by
transcription takes place in the nucleus of
host cell.

HIV Replication Cycle

Step 4: New viral RNA is used as
genomic RNA and to make viral
proteins

Viral RNA is transported out of the

nucleus of the host cell and used as
template for production of viral genomic
RNA and further translated into viral
proteins.
Cleavages of polypeptide by protease is
an enzyme that hydrolyzes or cuts
proteins and is important in the final steps
of HIV assembly and maturation.

HIV Replication Cycle

Step 5: Virus
maturation

release

and

New viral RNA and proteins move to cell

surface and a new, immature, HIV virus
forms.
The virus is released by budding out
through the host cell surface membrane
acquiring the lipoprotein envelope.
A matured virion is a single and complete
extracellular infective form of a virus that
consists of RNA with a envelope that
capable of infecting new host cells.

Immune dysfunction
Progressive depletion of CD4 T cells because of reduced production and
increased destruction. CD4 T cells are eliminated by direct infection, bystander
effects of syncitia formation, immune activation, proliferation and senescence.

Immune activation
Polyclonal activation of B lymphocytes
leading to hypergammaglobulinemia,
useless Ig G and IgA to irrelevant antigens
& autoantibodies.
Production of pro-inflammatory cytokines
(IL-6 & TNF-).

Allergic reactions due to immune

complexes (type 3 hypersensitivity), loss of
CD4 T cells responsible for producing
delayed-hypersensitivity allows outgrowth
of many opportunistic intracellular
infections manifestating AIDS (e.g.: fungi
and intracellular bacteria)