LECTURE THREE

HIV LIFE CYCLE

Expected Learning Outcomes

At the end of this lecture the learner should be able to:
1. Draw a detailed structure HIV
2. Discuss the life cycle of HIV
3. Explain pathogenesis of HIV & AIDS

THE STRUCTURE OF HIV VIRUS

HIV - A Retrovirus

A virus unique in the sense that: its genetic information is in form of RNA instead
of DNA. It contains the enzyme “reverse transcriptase,” which reverses the
central dogma for genetic information flow in cells from RNA to DNA and kills
helper lymphocytes upon infection.
HIV uses its RNA and the host’s DNA to make viral DNA. It has a long incubation
period. HIV consists of a cylindrical center surrounded by a sphere-shaped lipid
envelope. The center consists of two single strands of RNA. It utilizes the DNA of
CD4+ lymphocytes to replicate itself. Eventually destroys the CD4+ lymphocyte

Host cells infected with HIV have a very short lifespan. HIV continuously uses
new host cells to replicate itself. Up to 10 million individual viruses are produced
daily. During the first 24 hrs after exposure, the virus attacks. Within five days of
exposure, infected cells make their way to lymph nodes and peripheral blood,
where viral replication becomes very rapid.

Steps in HIV life cycle

There are 8 steps in the life cycle of Human Immunodeficiency Virus as described
by a scientist David Pier bone.

These stages include:

1. Viral attachment.
2. Viral penetration.
3. Uncoating.
4. Reverse transcription.
5. Integration.
6. Viral latency and protein synthesis.
7. Cleavage and viral Assembly.
8. Budding and Release.

Once the HIV virus is in the body, it targets and infects a certain type of
white blood cells called a CD4 cell. HIV then takes or “Hijacks” these cells
and turns them into factories that produce thousands of copies of the virus.
The steps that HIV goes through to complete this process are as follows:

Attachment (Binding), viral penetration and uncoating

HIV begins to enter a CD4 cell by binding (attaching) itself to a specific point
called a CD4 receptor, on the surface of the CD4. HIV must then bind to a second
co-receptor, either thCCR5 Co-receptor or the CXCR4 Co-receptor still on the
CD4 cell. This allows the virus to join with the CD4 cell in a process called
fusion. After fusion, HIV releases it RNA (Genetic Material) and enzymes
(proteins that cause chemical reactions) into the CD4 cell.
Reverse Transcription

HIV RNA (Genetic Material) contains the “instructors” that will reprogram the
CD4 cell so that it produces more viruses. In order to be effective, HIV’s RNA
must be changed into DNA. An HIV enzyme called reverse transcriptase changes
the HIV RNA into HIV DNA.

Integration

In this step, the newly formed HIV DNA enters the nucleus (Command Centre) of
the CD4 cell. Another enzyme called integrace combines or integrates HIV’s
DNA with the CD4 cell’s DNA.
Transcription

Once the virus has become part of the CD4 cells (is integrate into), it commands
the CD4 cell to start new HIV proteins. The proteins are the building blocks for
new HIV viruses. They are produced in long chains.

Assembly

An HIV enzyme called protease cuts the long chains of HIV proteins into smaller
pieces. As the smaller protein pieces come together with copies of HIV’s, RNA, a
new virus is put together (assembled).

Budding and Release

The newly assembled virus pushes (buds) out of the original CD4 cell by first
causing the CD4 to bulge. This burst open releasing the newly formed vivions out.
These new virions once released they target and infect other CD4 cells.
This cycle starts over and over again lowering the number of circulating CD4+ (T.
Helper cells) and hence weakening the immune system.
Disease Progression (Epidemiology)

 On first exposure, there is a 2-4 week period of intense viral replication

before the onset of an immune response and clinical illness
 Acute (short term) illness lasts from 1-2 weeks and occurs in 53% to 93% of
cases
 Clinical manifestations resolve as antibodies to the virus become detectable
in patient serum Patients then enter a stage of asymptomatic infection lasting
months to years (no symptoms)

Pathogenesis

HIV Infection
HIV virus initially infects cells just below the mucosal surface, Enters the local
immune cells and Infiltrates deeper tissues. Within 48 to 72 hours after inoculation,
HIV can spread to local lymph nodes; Virus everywhere in body, including blood
after about 7 days (range, 4 to 11 days). HIV then infects the CD4 cells and forces
the CD4 cell to make more HIV virus Immune system starts fights off the HIV by
destroying HIV infected cells
HIV Dynamics
10 billion HIV virus particles are produced and cleared daily in an infected
individual. Generation time is approximately 2 days.
2 billion CD4+ cells are destroyed each day. The entire supply of CD4 cells
turns over every 15 days

HIV: Initial Infection

HIV Pathogenesis

Once HIV gets to the blood, it settles into lymphoid organs and the central
nervous system
Target Cells for HIV

 Immunity cells:
o CD4+ T cell
o Monocyte-macrophage
o Langerhans cells skin
o Follicular dendritic cells
 Brain cells
 Gut cells of intestines
 Epithelial cells of intestine and vagina
 HIV Dynamics
After several months or years, the body cannot fight as well, because the very
cells used to fight (CD4+ cells) are being destroyed by the virus.

HIV Immune Deficiency

Progressive depletion in the numbers of circulating CD4+ cells is the hallmark
of HIV infection.

Stages of HIV

HIV Attacks the Immune system

In HIV infection, CD4 cells are attacked and killed. With time, severe losses of
CD4 cells make the body unable to fight off infection.

Stages of HIV infection

 Early Infection
 Window period
 Asymptomatic
  Symptomatic stage
 AIDS

Early Infection

The moment the virus gets into the body

Time between infection & enough antibodies for a positive HIV test
 Many people have no symptoms
 rash, sore throat, flu-like
o Acute retroviral syndrome
o Fever, Symptoms last 2-4 weeks, then resolve without treatment
 Window Period
o HIV infection has occurred
o HIV test negative
 Can spread HIV at this stage

Window Period
Duration: approximately 3 months. No symptoms or signs of illness
(asymptomatic). HIV test is negative. Virus is multiplying rapidly therefore
viral load is high. Person is very infectious.

Sero-conversion
Point at which HIV test becomes positive. Body starts making antibodies to
HIV a few weeks after infection. HIV test becomes positive when antibody
levels are high enough to be measured. Happens in about 3 months after
infection. Person may have a mild flu-like illness, lasting a week or two.
Afterwards, the person is well again.

Asymptomatic Period
Time period between sero-conversion and onset of HIV/AIDS-related illness.
Duration variable: < 1 year to > 15 years. Most people remain healthy
(asymptomatic) for about three years. Duration may depend on socio-economic
factors. The CD4 count is above 500 cells/ml.
 HIV test positive
 No symptoms
 Look good
 Feel good
 Can spread HIV
 HIV is damaging the immune system
Symptomatic period
Immune system is beginning to be impaired and CD4 count 500-200
Body is vulnerable to some, but not all infections:
 Tiredness, Fever, Diarrhea, Cough, Large glands, Rashes, Yeast
infections

CD4 count
Number of CD4 cells in blood provides a measure of immune system damage
which reflects phase of disease

CD4 count:
500 – 1200: Normal
200 – 500: Beginning of HIV illness
< 200: AIDS

AIDS
Immune system is very weak and CD4 count is <200, Viral load is high & the
person is very infectious.
The body is vulnerable to opportunistic infections
Symptoms depend on which opportunistic infection is present
Common symptoms:
 Fever > 1 month
 Soaking night sweats
 Weight loss > 10%
 Diarrhea > 1 month
 Severe weakness > 1 month
 Cancers
 Wasting syndrome
 Bed ridden
 Re-Infection

Different strains of HIV exist within the same HIV type. It is possible to be re-
infected with a different strain. When re-infection occurs, the immune system is
weakened more rapidly. Therefore, people with HIV are advised to use
protection (condom) when engaging in sexual activity.

SUMMARY
In this lecture we have focused on structure of HIV and its life cycle. It further
discusses HIV disease progression, pathogenesis and its relationship with the
immune system.

Further reading
Hardy D. 2017. Fundamentals of HIV Medicine.

Activity
25 years old Clement is a construction worker, who was laid off when the project
he was working on was discontinued due to the present economic crisis. He was
extremely worried about how he was going to provide for his family without a job.
He was basically against the idea of using heroin but learned through his friends
that he could make enough money to support his family by selling it on the
street. Clement occasionally tried the drug and was often supplied with syringes
by the people from whom he was buying the heroin. Two months ago Clement
tested HIV-positive. His wife eventually left him and returned with the children
to her hometown. He has been unable to contact her since. Clement increased his
heroin use as he felt that it couldn't be worse than the fact that he was already
infected. Besides, he enjoyed the temporary relief from his problems that the drug
provided.
Evaluation.
Discuss Clements behavior, giving details of possible ways through which he
could have escaped from getting infected by the Human Immuno-deficiency Virus.
Do you ascertain to Clément’s wife behavior? Discuss.
1. In your view, what is likely to become of Clement and why?