HIV VIRUS

Human Immunodeficiency Virus (HIV)

What is HIV?
• HIV stands for ‘human immunodeficiency virus’. It weakens a
person’s immune system by destroying important cells that
fight against disease and infection.
• HIV is a member of the genus Lentivirus, part of the family
Retroviridae.
• It is the causative agent of AIDS.
• AIDS AIDS stands for acquired immunodeficiency syndrome,
and it's the most advanced stage of HIV infection. It's
characterized by a weakened immune system that makes it
difficult for the body to fight off infections and certain cancers.
• Without treatment, average survival time after infection with
HIV is estimated to be 9 to 11 years, depending on the HIV
subtype.
Morphology of virus
Shape and size
• HIV is a spherical enveloped virus about 90-120nm in
diameter.
Envelope:
• HIV is enveloped virus. The envelope is a lipid bilayer
surrounding the viral matrix, which is derived from host cell
membrane during budding.
• Below the envelope, there is an icosahedral shell called
matrix (P17).
Genome:
• HIV is ss RNA virus. The genome consists of two identical
copies of positive sense Single stranded RNA genome.
• In association with viral RNA is the reverse transcriptase
enzyme
• The virus core is surrounded by a nucleocapsid composed
of protein(P24).
• Genome of HIV consists of 9 gene, 3 structural gene and 6
non-structural gene (regulatory gene).
• Structural gene (env, gag and pol), regulatory gene
(tat,rev,nef,vif,vpr and vpu in HIV-I and vpx in HIV-2)
• Enzymes:
• Reverse transcriptase (RNA dependent DNA polymerase)
• Protease
• Intrigase
• Ligase
Replication:
• Cell specific (CD+T cell)
• Virus entry: receptor mediated (gp120 and gp41)
• RNA Replicates to form DNA intermediate by Reverse
transcriptase enzyme
• Provirus remains permanently associated with host cell
• Release; budding
• Other properties:
• Oncogenic
• Mutation
• Species specific
• Family: Retroviridae
HIV genome and antigens
HIV has two identical copies of +SS RNA genome. The genome consists
of 3 structural gene and 6 regulatory gene. The product of these genes,
both structural and non-structural acts as antigens.
A. Structural gene; env, gag and pol gene
B. Regulatory gene; tat, rev, nef, vif, vpr and vpu in HIV-I and vpx in
HIV-2)
1. Structural gene:
i. Gag gene:
• Gag gene encodes for core and shell proteins of the virus
which is expressed as the precursor protein P55.
• This precursor protein is cleaved into 3 proteins by viral
protease to form P15, P18 and P24.
• P24 is the major core antigen and can be detected in serum
during the early stages of infection till the appearance of
antibodies.
ii. Pol gene:
• Pol gene encodes for the reverse transcriptase and other viral
enzymes.
• It is expressed as the precursor protein P100 which is cleaved
to form p31, p51 and p64.
iii. Env gene:
• Env gene encodes the precursor protein gp160 which is
cleaved to form surface spike glycoprotein (gp120) and
transmembrane protein (gp41).
• Genetic variety of HIV strain resides in env.
• The spike glycoprotein is the major envelope antigen and
are the first to appear after HIV infection
2. Non- structural and Regulatory gene:
i. Tat gene: ( transactivator of transcription)
• It encodes transactivator protein (P14) which promotes the
transcription of viral genome.
ii. Rev gene: (regulatory of expression of viral protein)
• It encodes Rev protein (P19) and promotes the expression
of viral structural proteins.
iii. Nef gene: ( Negative expression factors)
• It encodes precursors protein P27
• It is responsible for the regulation of latent state of virus.
iv. Vif gene: (Virion infectivity factor)
• It encodes the precursor protein p23 and promotes the
viral infectivity.
v. Vpr gene:
• It encodes the precursor protein P15.
• It stimulates promotor region of the virus.
vi. Vpu gene in HIV-I / Vpx gene in HIV-II
• It encodes the precursor protein P16.
• It promotes maturity and releases of progeny virus from
host cell.
How Is HIV Transmitted?
1. Sexual contact
• Most commonly, people get or transmit HIV through sexual
behaviors among homosexual and heterosexual individuals.
• HIV has been isolated from semen, vaginal and cervical
secretions and breast milk which are important vehicle of
transmission.
2. Parenteral transmission
• It may occur through blood after receiving infected blood
transfusion, blood products, sharing contaminated syringes
and needles as in intravenous drug absers or accidental
inoculation.
3. Perinatal transmission
• Infection may be transmitted from an infected mother to her
child either transplacentally or perinatally.
Pathogenesis
• After entry into blood stream, HIV comes into contact with
suitable host cells principally the CD4 lymphocytes.
• In the cell, once RNA is transcribed by reverse transcriptase
into DNA (provirus). The provirus is integrated into the
genome of the infected cell causing a latent infection.
• The long and variable incubation period of HIV infection is
because of the latency.
• From time to time lytic infection is initiated and release
progeny virions to infect other cells.
• In an infected person ,HIV can be isolated from blood,
lymphocytes, cell free plasma, cervical secretions, semen,
saliva, urine, tears and breast milk.
• The infection causes damage to the CD4 lymphocyte. CD4 cells
are depleted in numbers and the CD4: CD8 (helper:
suppressor) ration is reversed.
• Viral infection can suppress the function of infected cells
without causing any structural damage.
• This leads to a marked damping effect on cell mediated
immune response.
• Function of other cells (monocyte, macrophages) is also
affected due to the lack of secretions of activating factors by
CD4 cells.
• Clinical manifestations in HIV infections are mainly due to
failure of immune responses which leads to life threatening
opportunistic infections and malignancies.
• Dementia and other neurological lesions may also be seen in
AIDS. These may be due to direct effect of HIV on the central
What Is the main target for HIV?
• HIV infects vital cells in the human immune system, such as
• Helper T cells (specifically CD4+ T cells),
• Macrophages, and Dendritic cells.
• Therefore it weakens the immune system and leads to
other opportunistic infections.

Normal range
CD4 cell (helper T cell)- 500- 1200/mm3
CD8 cell (cytotoxic T cell)-150- 1000/mm3
CD4: CD8 ratio= 2:1
Incubation Period
• After successful invasion of HIV into the human body, HIV
antibody occurs within 4–8 weeks, followed by its
incubation period lasting 2–10 years.
• During this period, HIV still replicates constantly to
compromise the immune system, with gradually decreasing
CD4 T lymphocytes and infectivity.
• Even though the patients show no clinical symptoms, they
as HIV carriers, can spread the virus via various
transmission routes.

Window period:
• It is the time period between the initial infection of HIV and
the time when the body produced enough HIV antibodies
to be detected by HIV antibody test.
Clinical Characteristics
• The progression of HIV infection is a long-term natural
developing process.
• The patients survival duration depends on the quantity
of HIV in the body, individual health difference,
nutritional status and the effectiveness of the
therapies.
• HIV induces exhaustion and death of T cells, which is
demonstrated by decreased CD 4 T lymphocytes count.
• Clinically, the progression of HIV infection can be
divided into three stages, namely acute stage,
asymptomatic stage and AIDS stage.
1 Acute Stage
• After preliminary HIV infection, the HIV infection progresses into
acute stage in 2–4 weeks.
• Some patients show symptoms of HIV related viraemia and acute
immunity impairment.
• Most patients have slight clinical symptoms that are relieved after
1–3 weeks.
• The most commonly found symptom is fever, with accompanying
sore throat, muscle pain, headache, nausea, vomiting, skin rash,
thrush, arthralgia, splenohepatomegaly, enlarged lymph nodes,
weight loss and nervous system symptoms.
• Some patients may also have slight leukocytopenia,
thrombocytopenia or liver malfunction.
2 Asymptomatic Stage
• During the stage, no clinical manifestation can be found, while 40–
60 % patients may have specific lymphadenitis, predominantly
3 AIDS
• AIDS stage is the final stage of HIV infection. The patients
usually have obviously decreased CD4 T lymphocytes count
of lower than 200/μl, obviously increased HIV virus load in
plasma.
• During this period, the clinical manifestations include HIV-
related symptoms, various opportunistic infections and
neoplasms.
1.Persistent irregular fever of above 38 °C for more than 1
month, with no cause found;
2.Diarrhea (bowel movement more than three times daily),
persistent more than 1 month;
3.Weight loss over 10 % in 6 months;
4.Recurrent attacks of oral candidiasis albicans;
• The signs and symptoms of some of these infections may
include:
• Sweats
• Chills
• Recurring fever
• Chronic diarrhea
• Swollen lymph glands
• Persistent white spots or unusual lesions on your tongue or
in your mouth
• Persistent, unexplained fatigue
• Weakness
• Weight loss
• Skin rashes or bumps
 HIV disease progression –
clinical latency
AIDS and
Primary Acute Asymptomatic Death
infection (clinical latency)
Levels (Separate Scales)

CD8+ T cell HIV viral load

Neutralizing Antibodies

CD4+ T cell
4–8 Years
weeks
 Laboratory Diagnosis of HIV
 Clinical specimen
Blood, Urine, Saliva, lymphnode biopsy.
1. Hematological/ Immunological test:
 Total leucocytes and lymphocytes count to demonstrate
leucopenia and lymphocytes count usually less than
2000mmᶾ. The CD4 count progressively decreased
below 200 cubic milliliter of blood.
 Determination of CD4:CD8 cell count:- the value will be
reversed in case of AIDS patient.
 Platelets count will show thrombocytopenia.
 IgA and IgG level raised
Screening test

• Most commonly used test are:

ELISA
Cassette ELISA
Immuno-chromatographic strips
Coated particle agglutination
Immunoperoxidase
Dip sticks test
Tri Dot card for HIV
• Among them ELISA is an ideal screening test of HIV.
Specific test for HIV infection
 These includes the demonstration of HIV it’s antigens
or the components and antibodies and isolation of
virus.
Antigen detection
• Core antigens p24 antigen is the earliest viral markers
to be appear in blood.
• The p24 antigen capture assay using anti-24
antibodies as the solid phase can be used for the
detection of the antigens.
Antibody detection
• Ab takes about 2-6 months to appear following the
sexual exposure.
• IgM and IgG can be detected in patients sera.
• Demonstration of antibodies is the simplest and most
widely employed techniques for the diagnosis of HIV
infection.
• The serological test for detection of anti-HIV
antibodies are two types:
Screenings: HIV Rapid card test, HIV tridot, ELISA
Confirmatory test : Western blot test
Viral Isolation
• Once the person infected with HIV virus the persons
remain infected through out the life. Virus can be
isolated from the blood circulation and several body
secretions such as breast milk, saliva, semen etc,
peripheral lymphocytes and many parts of body. The
techniques for the isolation is by co-cultivation of
patients lymphocytes with uninfected lymhocytes in
the presence of interleukin-2. Virus replication can
be demonstrated by the demonstration of reverse
transcriptase activity as well as p24 antigen
detection.
• However viral isolation is not suitable as a routine
diagnostic test.
Molecular method/ Nucleic acid detection
• PCR become the gold standard for the diagnosis in all
the stage of HIV infection
• PCR can be used for the diagnosis as well as
monitoring the level of viremia / monitoring the viral
load in patients blood.
 Western Blot Technique
• The confirmatory test commonly employed is the western blot
test.
• In this test HIV proteins are separated according to their
electrophoretic motility by polyacrylamide gel electrophoresis.
• The polyacrylamide gel electrophoresis are blotted in
nitrocellulose strips. The nitrocellulose strips are reacted with test
sera and then with enzyme conjugated antihuman globulin.
• A suitable substrate is the added which produce the prominent
color band where the specific antibody has reacted with separated
viral protein.
• The position of band on the strips indicates the antigens with
which the antibody has reacted.
• In the positive serum bands will be seen with multiple proteins
typically p24.
 The test may considered positive even if it shows
bands against at least two of the following gene
products such as p24, gp41, gp120, and gp160.

 Disadvantage:
1. It is time consuming.
2. It is costly.
Prevention and controls of AIDS
1. Providing the sex education and make the people
awareness about the diseases.
2. Using the femidom and condom by female and male
while having a sex with mutiple partners.
3. Screening of blood and blood products before any
transfusion
 Treatments
Drugs name Mode of action
1. Zidovudine Reverse transcriptase inhibitors
2. Azidothymidine Nucleoside or non nucleoside analogues
3. Didanosine
4. Zalcitabine
5. Lamivudine
1. Saquinaivir Protease inhibitors
2. Ritonavir
3. Indinavir
1. Fuzeon Fusion inhibitors
2. Enfuvirtide
1. Rateqravir Intergrase inhibitors
 HAART[Highly Active Antiretroviral Therapy]

• A combination of 3 or more anti-HIV drugs

taken at the same time.
• Two nucleoside analogues and single protease
inhibitors.
• Fusion inhibitors such as fuzeon, Enfurvirtide.
• Intregrase inhibitors: Rateqravir.
 Post-exposure prophylaxis[PEP]
• PEP involves the taking anti-HIV drugs as soon as possible
after the exposure to HIV. The drugs reduces the chance of
becoming the HIV positive. These medication keeps HIV
from copies itself and spreading through your body.
• To be effective PEP must begins within 72hrs of exposure
before the virus has time to rapidly replicate in the body.
• PEP consist of 2-3 anti retroviral medications and should be
taken for 28 days your doctor will determine what the
treatment is right for you based on how you were exposed
to HIV.
• PEP is not 100% effective it doesnot guarantee that
someone exposed to HIV will not become infected with HIV.