Pathogenesis of HIV,virus entry and mechanism of infection, its effect on human body.

1. Rajani A. Prabhu
MI-1414
MSC-II
Virology ISA II
PATHOGENISIS OF AIDS

2. INTRODUCTION
 HIV is a member of the lentivirus family, a
subgroup of retroviruses, RNA viruses that
replicate via a DNA intermediate.
 AIDS: acquired immunodeficiency syndrome
 AIDS is defined by a loss of CD4 T lymphocytes
or the occurrence of opportunistic infections or
cancers.

3. MORPHOLOGY

4. GENOME OF HIV

5. GENOME OF HIV
 The genes of HIV in the virion(RNA) and
integrated into host cell genome (DNA).
 There are two types of genes analyzed-
 a) Structural genes encode for products which
participate in formation of functional structure of
virus
1) gag gene
 encodes for core and shell of virus.
 The p24 antigen (major core antigen) can be
detected in serum during the early stages of
infection till the appearance of the antibodies.

6. GENOME OF HIV
 2) pol gene
 Encodes for the polymerase, reverse
transcriptase and other viral enzymes such as
protease and integrase.
3) env gene
 determines the synthesis of envelop glycoprotein
gp 160 which is cleaved into gp 120 and gp41.
 The antibodies to gp 120 are the first to appear
after HIV infection and are present in circulation
till the terminal stage of infection

7.  b) Non structural and Regulatory genes
1) vif - (Viral infectivity factor gene) influences
infectivity of viral particles.
2) vpr-stimulates promoter region of the virus
3) vpu (in HIV-1 ) and vpx (in HIV-2)

8. PATHOGENESIS
 Infection is transmitted when virus enters the
blood or tissues of a person and comes in to
contact with a suitable host cell, principally the
CD4 lymphocytes.
 The virus may infect any cell bearing the CD4
antigen on the surface.
 Primarily these are the CD4 + helper T
lymphocytes.

9. CELLS AFFECTED
 Lymphoreticular system:
 CD4+ T-Helper cells
 Macrophages
 Monocytes
 B-lymphocytes
 Certain endothelial cells
 Central nervous system:
 Microglia of the nervous system
 Astrocytes
 Oligodendrocytes
 Neurones

11. STEPS OF VIRAL ENTRY INTO
HOST CELL
 ATTACHMENT OF VIRUS INTO THE HOST
CELL –Specific binding of the virus to the CD4
receptors is by the envelop glycoprotein gp120.
 VIRUS TO CELL FUSION – For infection to take
place the cell fusion is essential.
o This is brought about by the transmembrane
glycoprotein gp 41. HIV-1 utilizes two major co-
receptors along with CD4 to bind to, fuse with,
and enter target cells; these co-receptors are
CCR5 and CXCR4, which are also receptors for
certain endogenous chemokines.

12.  UNCOATING OF THE VIRAL ENVELOPE AND
ENTRY OF NUCLEAR CAPSID CORE INTO
THE CELL
o After fusion of virus with the host cell membrane,
HIV genome is uncoated and internalized in to
cell.
o Viral RNA is released into the core cytoplasm

13.  VIRAL TRANSCRIPTION
o viral reverse transcriptase mediates
transcription of its RNA;
o RNA-DNA hybrid is formed.
o Original RNA strand is degraded by ribonuclease
H, followed by
o synthesis of second strand of DNA to yield
double strand HIV DNA

14.  INTEGRATION INTO THE HOST DNA AS
PROVIRUS
o The double stranded DNA is integrated in to the
genome of the infected host cell through the action of
the viral integrase enzyme, causing a latent infection.
 Fate of provirus
o From time to time, lytic infection is initiated releasing
progeny virions, which infect other cells.
o The long and variable incubation period of HIV is
because of the latency.
o In an infected individual the virus can be isolated from
the blood, lymphocytes, cell free plasma, semen,
cervical secretions, saliva, urine and breast milk.

16. STEPS OF VIRAL EXIT FROM
HOST CELL
 TRANSCRIPTION BACK INTO RNA
o The viral DNA is transcribed into RNA and
multiple copies of viral RNA are produced.
o There are only nine genes in HIV RNA, and these
code for the production of structural proteins,
accessory proteins, and enzymes essential for
the virus's replicative cycle.

17.  VIRION ASSEMBLY - With the help of viral
protease, the new virions are assembled into the
polypeptide sequences needed for HIV virion
formation and infectivity.
 CELL LYSIS- The infected cell is made to burst
open, presumably by the action of cellular
proteins.

18. Stages of AIDS
 HIV infection can generally be broken down into
four distinct stages: primary infection, clinically
asymptomatic stage, symptomatic HIV infection,
and progression from HIV to AIDS.

19. Acute HIV infection
 Primary infection also can be said as acute
stage of infection.
 This stage of infection lasts for a few weeks and
is often accompanied by a short flu-like illness.
 The virus attacks and destroys the infection-
fighting CD4 cells of the immune system.
 HIV can be transmitted during any stage of
infection, but the risk is greatest during acute HIV
infection.

20.  This phase is also called window period or
phase of Sero conversion.
 There is production of
CD8+ cells which kills HIV
Infected cells.
 Some patients do not
develop symptoms after
they first get infected with
HIV.

21. Chronic HIV infection
 The second stage of HIV infection is chronic HIV
infection (also called asymptomatic HIV
infection or clinical latency.)
 During this stage of the disease, HIV continues to
multiply in the body but at very low levels.
 People with chronic HIV infection may not have
any HIV-related symptoms, but they can still
spread HIV to others.
 The patients show positive antibody tests
during this phase.
 Without treatment with HIV medicines, chronic
HIV infection usually advances to AIDS in 10 to
12 years.

22. Symptomatic infection
 Over time the immune system becomes severely
damaged by HIV. This is thought to happen for
three main reasons:
 The lymph nodes and tissues become damaged
or 'burnt out' because of the years of activity.
 HIV mutates and becomes more pathogenic, in
other words stronger and more varied, leading to
more T helper cell destruction.
 The body fails to keep up with replacing the T
helper cells that are lost.

23.  Symptomatic HIV infection is mainly caused by
the emergence of certain opportunistic
infections that the immune system would
normally prevent.
 This stage of HIV infection is often characterised
by multi-system disease and infections can occur
in almost all body systems

24. 0PORTUNISTIC INFECTIONS IN
AIDS

25. AIDS
 As the immune system becomes more and more
damaged the individual may develop increasingly
severe opportunistic infections and cancers,
leading eventually to an AIDS diagnosis.
 When the CD4 lymphocyte count drops below
200/microliter, then the stage of clinical AIDS has
been reached.

26. Mechanism of CD4 T cell depletion in
HIV infection

27. Cause of immunodeficiency

28. EFFECTS
 Monocyte, macrophage system is also affected
apparently due to the lack of the activating factors
by the T4 lymphocytes.
 The activity of NK cells and Tc (T Cytotoxic) cells
are also affected.
 The clinical manifestations are due to failure of
the immune responses.
 This renders the patient susceptible to life
threatening opportunistic infections and
malignancies.

29.  The most prominent effect of HIV is its T-helper
cell suppression and lysis leading to the familiar
AIDS complications.
 Infection of the cells of the CNS cause acute
aseptic meningitis, subacute encephalitis,
vacuolar myelopathy and peripheral neuropathy.
Later it leads to even AIDS dementia complex.
 The CD4-gp120 interaction is also permissive to
other viruses like Cytomegalovirus, Hepatitis
virus, Herpes simplex virus, etc. These viruses
lead to further cell damage i. e. cytopathy.

30. Disease progression through
different phases in HIV infected
cases

31. references
 Interim WHO clinical staging of HIV/AIDS and
HIV/AIDS case definitions for surveillance – 2005.
 Pantaleo G (1993) New concepts in the
immunopathogenesis of human
immunodeficiency virus infection. N Engl J Med.
328(5):327-35.
 Piatak M., M.S Saag, L.C Yang, S.J Clark, J.C
Kappes, K.C Luk, B.H Hahn, G.M Shaw and J.D
Lifson (1993) High levels of HIV-1 in plasma
during all stages of infection determined by
competitive PCR. Science 259 (5102): 1749–
1754.

32. THANK YOU….