RETROVIRUSES: HIV 51

I. RETROVIRUSES virus core is surrounded by a nucleocapsid composed

of protein. The virus contains a lipoprotein envelope.
These are RNA viruses that belong to family
The major virus coded envelope glycoproteins are the
Rotroriridae. Members of this family possess reverse
projecting spikes on the surface and the anchoring
transcriptase (RNA directed DNA polymerase)
transmembrane pedicles.
enzyme which prepares a DNA copy of the RNA
genome in host cell. The presence of enzyme reverse B. Modes of Transmission
transcriptase is a characteristic feature.
There are three modes of transmission: sexual
contact, parenteral and perinatal.
I1. HUMAN IMMUNODEFIIENCY 1. Sexual contact: This is the most important mode
VIRUS (HIV) of transmission. Sexual transmission occurs
HIV occurs in two main types, HIV-1 and HIV-2. among both homosexual as well as heterosexual
individuals.
A. MorphologY 2. Parenteral transmission: It may occur through
HIV is a spherical enveloped virus, about 90-120 nm blood after receiving infected blood transfusions,
in diameter (Fig. 51.1). It contains two identical copies blood products, sharing contaminated syringes
of single stranded RNA genome. In association with and needles as in intravenous drug abusers or
viral RNA is the reverse transcriptase enzyme. The accidental inoculation.

Envelope glycoprotein spike (gp 120)

Envelope

RNA
Nucleocapsid (p24)
Outer shell of nucleocapsid (p 18)
Reverse transcriptase

Transmembrane pedicle glycoprotein (gp 41)

Fip 51 d i c i o n c i t tiruS
 306 Unit IV Virology

3. Perinatal transmission: Infection may be breakdown of immune defence mechanism.

transmitted from an infected mother to her of the with HIV disease die of
child either
patients infectio
transplacentally or perinatally. other than HIV eg. opportunistic
infections
C. Clinical Features malignancies (Table 51.2). AIDS is the end sta ande of
HIV infection.
HIV infects all cells
expressing at their surface the CD4
antigen, which is the receptor for the virus. It infects Table 51.2:
primarily the CD4+ lymphocytes. The Centre for Opportunistic Infections and Malignancies
Disease Control (CDC) in Atlanta, USA has classified
Commonly Associated with HIV Infection
I. Bacterial
the clinical course of HIV infection into
various groups
(Table 51.1).
1. Mycobacterial infections-Tuberculosis and
non-tuberculous infections
2. M. avium complex
Table 51.1: Classification
System for HIV Infection
3. Salmonellosis
and AIDSS
(Centre for Disease Control, USA) II. Viral

Group I 1. CMV
Acute HIV infection
2. Herpes simplex
Group II Asymptomatic infection 3. Varicella-zoster
Group III Persistent generalised 4. Epstein-Barr (EB) virus
lymphadenopathy III. Mycotic
Group IV
1. Pneumocystis jiroveci pneumonia
Subgroup A Constitutional disease -ARC 2. Candidiasis
abgroup B Neurological diseases 3. Cryptococcosis
Subgroup C Secondary infectious diseases 4. Aspergillosis
C1 & C2
5. Histoplasmosis
Subgroup D Secondary cancers 6. Coccidioidomycosis

Subgroup E Other conditions IV. Parasitic

1. Toxoplasmosis
1. Group -Acute HIV infection: The illness is 2. Cryptosporidiosis
characterised by acute onset of fever, malaise, 3. Isosporiasis
sore throat, mylagia, arthralgia, skin rash and
4. Generalised strongyloidiasis
lymphadenopathy. V. Malignancies
2. Group l-Asymptomatic infection: This includes
all infected persons who 1. Kaposi's sarcoma
are
usually well.
They show positive HIV antibody tests, and 2. B-cell lymphoma or non-Hodgkin's lymphoma
are infectious.
3. Group lI1-Persistent generalised lympha-denopathy Oral Manifestations
(PGL: This group is characterised by enlarged
Patients with AIDS are at greater risk for
nodes. bacterid
viral and fungal infections of the mouth.
4. Group IV-Symptomatic HIV infection: When Denta
caries and gingivitis may occur. Acute necrotizing
CD4+ T lymphocyte count falls below 400 hat
per ulcerative gingivitis
may act
mms, the patient may develop symptoms like as an
indicato
the patient have AIDS.
may
fever, diarrhoea, weight loss, night sweats and as

opportunistic infections. Herpes simplex infections may be presen ts

multiple, deeper, more painful oral lesions in patte
When CD4+ cells fall below 200 per mm*, the titre with AIDS. These lesions heal slower than the herpe
of virus increases markedly and there is irreversible
simplex lesions in immuncompetent persoi
 Ch 51:
Retroviruses: HIV 307
Hair leukoplakia is an
early sign of
It appears HIV infected
nodeficiency.
nmunodefic
to be induced by persons remain negative tor
(EB) virus, possibly in combination
-barr antibodies during window
napillomavirus or Candida in patients with HIV replication takes place for period, when initial viral
about 2-3 weeks.
on The llesions are generally bilateral, white,
fection. There are two
excrescences on the
oft, hairy
ite
lateral screening and
types of
serological tests-
margins
ongue. However, unilateral, corrugated
of supplemental (Table 51.3).
lesions Table 51.3:
also occur elsewhere on the tongue Laboratory Tests for Detection of
or oral
Antibodies in HIV Infection Specific
UcOsa.
1.
Candidiasis may be present in most patients Screening (E/R/S) tests
(a) ELISA
ith HIV infection. Thrush is usually found on
palatal and buccal mucosae. Asymptomatic (b) Rapid tests
rvthematous lesions of candidiasis sometimes -

Dot blot assay

- Particle agglutination
ccur on the palatal and lingual mucosae. Other
ral manifestations include angular chelitis (fissures -

HIV spot and comb tests

nd ulcers at the corner of the mouth) and (c) Simple tests
nucocutaneous candidiasis. These are based on ELISA principle.
2. Supplemental tests
. Laboratory Diagnosis - Western blot test

. Specific Tests for HIV Infections - Indirect immunofluorescence test

i) Antigen detection Radio Immuno Precipitation assay
he p24 antigen is the earliest virus marker to
ppear in the blood. ELISA can be used for detection Screening tests
f this antigen. It may be useful for diagnosis in
(a) ELISA test: ELISA is the method most commonly
window period. used. It is highly sensitive and specific test.
ELISA test is an extremely good screening test
) Virus isolation
and most laboratories use a commercial ELISA
isolated. It can
for diagnosis, virus is not routinely of kit that contains both HIV-1 and HIV-2.
De isolated from CD4 lymphocytes peripheral alternative to serum for
Virus isolation is
Saliva is an acceptable
bone-marrow and serum.
blood, antibody testing by ELISA.
test for diagnosis in window period
an important absent in serum of patient. (b) Rapid tests: These tests take less
than 30 minutes
when antibodies are
and do not require expensive equipment. The

ii) Detection of viral nucleic acid rapid tests include dot-blot assay, particle
HIV spot and comb tests.
agglutination,
Viral nucleic acid be detected by polymerase
can
tests: They take 1-2 hours and do not
test is highly
sensitive (c) Simple
Chain reaction (PCR). The in require expensive equipment.
and It is also useful for diagnosis
specific.
window period. Supplemental tests

Western blot test: In this test,

HIV proteins are

iv) Antibody detection (a) electrophoresis.

and
gel
separated by polyacrylamideblotted
is the simplest on to strips
emonstration of antibodies The separated proteins
are

technique for diagnosis. These strips are reacted

st commonly employed
nitrocellulose paper.
of
months for
antibodies
Antibodies to HIV proteins, if
nay take several weeks to with test sera. different
antibodies appear combine with
after infection. IgM in test serum,
aPpear weeks after
infection, to present
HIV. The position
of the colour band
irst usually in about 3-4 fragments of
be
followed by IgG antibodies.
 E.
Prevention

following
preventive measures
The
r e c o m m e n d e d .

The use of condoms an

. Sexual
contact: prever
virus.
transmission
of the
Contaminated
2. Sharing needles: syringes
should not be
shared.
needles
blood and blood products are to b.
3 Blood: All
p 160
This also applies to tion o
p 120 Screened for HIV.
semen,
marrow, kidney and otherorgans
cornea,

patient and initiation

of AlDS
4. Isolation
p41 treatment.
Screening of individual
5. Control of infecfion:
within risk groups helps to identify the HIL
p 24
infected persons.

18
F. Prophylaxis
vaccine has yet been found out. High
No effective
of Western blot
test for HIV of the virus has made difficulty ir
Fig. 51.2 Dlagramatic representation rate of mutation
developing the vaccine.

on the strip indicates the fragment of antigen

have reacted (lig.
51.2).
Therapy (ART)
with which antibodies G. Antiretroviral
one screening
test may with antiretroviral drugs is the
A positive result in any Specific treatment
without confirmation. It
was
of HIV infection
not be accepted
for mainstay in the management
to use the Western blot test active antiretroviral therapy (HAART)
the practice Highly
confirmation. As the test is
cumbersome, costly inhibition of HIV replication ine
effective in
and not readily available,
different strategies are of the HIV-infected individuals but major
most
n o w is to
followed forconfirmation. The practice drawback with this therapy is
the selection o
different types of ELISA or drugs include-
perform either two resistant mutants. Antiretroviral
tests. A serum
an ELISA with any of the rapid non-nucleoside inhibitors
both nucleoside and
in both tests is considered positive.
positive of enzyme transcriptase, viral pretease
reverse

Indirect immunofluorescence test: HIV infected inhibitor and

(b) inhibitors, fusion inhibitor, integrase
cells are fixed onto glass slides and then reacted inhibitor(Table 51.4). These drugs
have been
with serum followed by fluorescein conjugated entry
used as monotherapy or in various combinations
antihuman gamma globulin. In a positive Adverse reactions and high cost restrict their wu
test, apple-green fluorescence appears when use in developing countries.
examined under fluorescent microscope. specific antiretroviral therapy
Apart from incluc u d e

2. Non-specific Tests other measures in the of AIDS

treatme ustic

(i) Total and differential leucocyte count

(i) treatment and prophylaxis of opportu and

In AIDS, there is leucopenia with a infections and tumours (ii) general management
lymphocyte count less than 400 per mm (ii) immunorestorative measures.

(ii) T-lymphocyte subset assays

The normal CD4: CD8 T-cell ratio of 2: 1, H. Postexposure Prophylaxis (PEP) 7hally

is reversed to 0.5: 1 in cases of AlDS. The Exposure to blood, body fluid, other poterd contaminate

count of CD4 lymphocy tes falls below 200 infected material or an instrument o f

to ris.
per mm. with one of these materials may lead