PATHOGENESIS OF HIV
AFMG:344
ADIL KHAN
GUIDED BY:
DR. SANJEEV SEHGAL
PATHOGENESIS
MODE OF TRANSMISSION
HIV is transmitted through the following modes.
1.Sexual modeis by far the most common mode of
transmission, accounts for 75% of total cases in the
world
„Heterosexual route (male to female via vaginal
coitus) is the commonest mode
„However, the risk of transmission through sexual
route is minimal (0.1–1% per coitus)
„Anal intercourse (among homosexual males or
even
male to female) has higher risk of transmission
than
vaginal intercourse.
„Blood transfusion is the least common mode of
transmission (5%) but the risk of transmission is
maximum (90–95%).
„Percutaneous/mucosal transmission modes
such as needle stick injury, injection drug abuse
and sharing razors or tattooing or splashes of
infected blood on eyes, etc. are among the less
effective modes of transmission
„Perinatal mode: In the absence of any
intervention, the risk of transmission from mother
to fetus is about 20–40% „Transmission may
occur at any time during
pregnancyandbreastfeedingbuttheriskismaximum
during delivery
„Risk is maximum if mother is recently infected or
has
already developed AIDS.
„There is no evidence of HIV transmission by
casual
contact or kissing or insect bite
„Viral load is maximum in blood, genital
secretions, and
CSF; variable in breast milk and saliva; zero to
minimal
in other body fluids or urine and glycoproteins,
which prevent transmission of the virus.
„Saliva may contain inhibitory substances like
fibronectin
and glycoproteins, which prevent transmission
of the virus.
RECEPTOR ATTACHMENT
The following receptor interaction is essential for
HIV entry into the host cell.
„Main receptor: HIV enters into the target cells by
binding
its gp120 to the CD4 receptor on host cell surface.
CD4 molecules are mainly expressed on helper T
cells; and also on the surface of various other
cells like monocytes, macrophages, Langerhans
cells, astrocytes, keratinocytes and glial cells
„A second co-receptor in addition to CD4 is
necessary for fusion of HIV to gain entry into
the host cell. Usually, the chemokine receptors
act as co-receptors for HIV and act by binding
to gp120. Examples include:
„CXCR4 molecules present on T lymphocytes
„CCR5 molecules present on cells of
macrophage
lineage.
„DC-SIGN, a dendritic cell-specific lectin
receptor present
in skin and mucosal surfaces, can also bind to
HIV-1 but does not mediate cell entry. Rather,
it may facilitate transport of HIV by dendritic
cells to lymphoid organs where HIV replicates
further in T cells.
REPLICATION
The replication of HIV occurs through the
following steps:
„Fusion: Following attachment of receptor and
co- receptor to gp120, fusion of HIV to host cell
takes place; mediated by the fusion protein
gp41
„Penetration and uncoating: After fusion, HIV
nucleocapsid enters into the host cell cytoplasm,
which is followed by uncoating and release of two
copies of ssRNA and viral enzymes
„everse transcription: Viral reverse transcriptase
R
mediates transcription of its ssRNA into ssDNA so
that DNA-RNA hybrid is formed. The RNA is
degraded by viral endonuclease and ssDNA
replicates to form dsDNA.
„Transcription of the DNA occurs to form some of
the components of viral proteins
„Pre-integration complex: The nucleoprotein
complex formed, comprises of linear dsDNA, gag
matrix protein, accessory vpr protein and viral
integrase. This is called pre-integration complex,
which is transported into the host cell nucleus
„Integration: The viral dsDNA gets integrated into
the host cell chromosome; mediated by viral
integrase. The integrated virus is called as provirus
„atency:In the integrated state,HIV establishes a
L
latent infection for variable period. However, HIV is
different from other latent viruses as it is able to
replicate even in latent state and is infectious to
other neighboring cells.
QUESTIONS
● Name four modes of transmission of HIV?
● HIV has a unique enzyme called?
● which route has the highest risk of transmission?
● GP120 binds to?
THANK
YOU