HIV is an abbreviation of Human Immunodeficiency Virus

A retrovirus that causes Acquired Immunodeficiency Syndrome (AIDS) by infecting CD4 cells of the immune system

The virus attacks the cells of immune system causing immune suppress

HIV: Infecting human beings.

Immunodeficiency: weakness of the body’s ability to fight off infections and illnesses.

Virus: A pathogen having the ability to replicate only inside the living cell.

HIV is the virus that causes AIDS.

Not everyone who is infected with HIV has AIDS.

Everyone with AIDS is infected with HIV.

AIDS is result of progression of HIV infection.

Anyone infected with HIV, although healthy.can still transmit the virus to another person.

Unprotected sexual contact with an infected partner.

Exposure to broken skin or wound to infected blood or body fluids.

Transfusion with HIV infected blood.

Injection with contaminated objects.

Mother to child during pregnancy, birth or breast feeding.

Time from initial infection with HIV until antibodies are detected by a single test.

Usually 3 – 8 weeks before antibodies are detected.

May test false negative for HIV antibodies during this time period.

Can still pass the virus to others during this period

HIV is a member of a family known as Retroviruses (Retroviridae)

Retroviruses consist two pieces of single strand RNA as their genetic material

Retroviruses are unusual because they are capable of making copies of DNA from RNA hence their name retroviruses (backward transcription)

This is possible because they have a reverse transcriptase enzyme

HIV is a particle composed of lipid bilayer known as the envelope

In the lipid bilayer there are two glycoprotein called gp120 and gp41.

Inside the lipid bilayer, there is a core consisting proteins called p24 and p17

Inside the inner core, there are 2 pieces of single stranded RNA and important enzymes (reverse transcriptase, integrase and protease)

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p17 (matrix protein): forms the outer shell of the core of the virus, lining the inner surface of the viral membrane.

gp120 (envelope protein): a glycoprotein exposed on the surface of the HIV envelope.

gp120 is essential for virus entry into cells as it plays a vital role in seeking out specific cell surface receptors for entry.

gp41 (envelope protein): a glycoprotein that supports entry of HIV into the cell.

Reverse transcriptase (p64): a DNA polymerase enzyme that transcribes single-stranded RNA into double-stranded DNA. Normal transcription involves the synthesis of RNA from DNA; hence, reverse transcription is the reverse of this

Protease: HIV protease cleaves newly synthesized polyproteins at the appropriate places

to create the mature protein components of an infectious HIV virion. Without effective HIV PR, HIV virions remain uninfectious (defective virus).

Integrase: an enzyme produced by HIV that enables its genetic material to be integrated into the DNA of the infected cell. It is also produced by viruses containing double stranded DNAs for the same purpose.

p24 (core proteins): A major core protein of the human immunodeficiency virus.

In order for viruses to reproduce, they must infect a cell. Viruses are not technically alive: they are like a brain with no body. In order to make new viruses, they must hi-jack a cell, and use it to make new viruses. Just as your body is constantly making new skin cells, or new blood cells, each cell often makes new proteins in order to stay alive and to reproduce. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well. HIV mostly infects cells in the immune system.

Several different kinds of cells have proteins on their surface that are called CD4 receptors. HIV searches for cells that have CD4 surface receptors, because this particular protein enables the virus to bind to the cell.

Although HIV infects a variety of cells, its main target is the T4-lymphocyte (also called the “T-helper cell”), a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible for warning your immune system that there are invaders in the system.Once HIV binds to a cell, it hides HIV DNA inside the cell’s DNA: this turns the cell into a sort of HIV factory and replicates itself.

A virus consists of an outer envelope of protein, fat and sugar wrapped around a set of genes (in the case of HIV, genetic information is carried as RNA instead of DNA) and special enzymes.HIV has proteins on its envelope that are strongly attracted to the CD4+ surface receptor on the outside of the T4-cell. When HIV binds to a CD4+ surface receptor, it activates other proteins on the cell’s surface, allowing the HIV envelope to fuse to the outside of the cell.Entry can be blocked by entry inhibitors.

HIV’s genes are carried in two strands of RNA, while the genetic material of human cells is found in DNA. In order for the virus to infect the cell, a process called “reverse transcription” makes a DNA copy of the virus’s RNA.After the binding process, the viral capsid (the inside of the virus which contains the RNA and important enzymes) is released into the host cell. A viral enzyme called reverse transcriptase makes a DNA copy of the RNA. This new DNA is called “proviral DNA.”Reverse transcription can be blocked by: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

The HIV DNA is then carried to the cell’s nucleus (center), where the cell’s DNA is kept. Then, another viral enzyme called integrase hides the proviral DNA into the cell’s DNA. Then, when the cell tries to make new proteins, it can accidentally make new HIVs.Integration can be blocked by integrase inhibitors

Once HIV’s genetic material is inside the cell’s nucleus, it directs the cell to produce new HIV.The strands of viral DNA in the nucleus separate, and special enzymes create a complementary strand of genetic material called messenger RNA or mRNA (instructions for making new HIV).Transcription can be blocked by antisense antivirals or transcription inhibitors (TIs), new classes of drugs that are in the earliest stage of research

The mRNA carries instructions for making new viral proteins from the nucleus to a kind of workshop in the cell. Each section of the mRNA corresponds to a protein building block for making a part of HIV.As each mRNA strand is processed, a corresponding string of proteins is made. This process continues until the mRNA strand has been transformed or “translated” into new viral proteins needed to make a new virus.

The final step begins with the assembly of new virus. Long strings of proteins are cut up by a viral enzyme called protease into smaller proteins. These proteins serve a variety of functions; some become structural elements of new HIV, while others become enzymes, such as reverse transcriptase.Once the new viral particles are assembled, they bud off the host cell, and create a new virus. The virus then enters the maturation stage, which involves the processing of viral proteins. Maturation is the final step in the process and is required for the virus to become infectious.With viral assembly and maturation completed, the virus is able to infect new cells. Each infected cell can produce a lot of new viruses.Viral assembly can be blocked by Protease Inhibitors (PIs). Maturation, a new target of companies developing anti-HIV drugs, may be blocked using Maturation Inhibitors

HIV does not cause one disease condition but associated with a group of diseases and conditions

Main effect of HIV in the human is that it weakens the immune system hence rendering it incapable of fighting against diseases

Example of diseases associated with HIV can be grouped as follows:

Viral infections for example herpes virus infections and reactivation diseases.

Bacterial infections for example. Mycobacteria specie, salmonella, shigella, staphylococcal and streptococcal.

Fungal infections for example. Candida spp, Cryptococcus spp, Pneumocystis spp and histoplasma spp.

Parasitic infections, example Toxoplasmosis, strongyloidiasis, cryptosporidiosis.

Malignant conditions for example Kaposi’s sarcoma, Lymphoma, carcinoma of the cervix

HIV can also directly affect other organs of the body example brain, heart, kidney and skin.

Factors that may shorten the time between HIV and AIDS

Older age

HIV subtype

Co-infection with other viruses

Poor nutrition

Severe stress

Your genetic background

Factors that may delay the time between HIV and AIDS

Taking antiretroviral therapy

Staying in HIV care

Closely adhering to your doctor’s recommendations

Eating healthful foods

Taking care of yourself

Your genetic background

HIV can be diagnosed by the following ways

Specimen

Whole blood

Serum

plasma

dried blood spot and

Other body fluids

Serological Tests (rapid and ELISA test)

Detection of antibodies produced against by the virus

Detection of viral components for example p24

Detection of viral genetic material (RNA)

Management of HIV includes treatment of the associated infections or conditions and specific treatment to control the HIV (HIV can not be cured but just controlled).

All the drugs used in HIV target the enzymes used in the viral replication cycle

Treatment involves simultaneous use of more than one drug of different classes

Drugs used to treat/control HIV can be divided into classes as follows:

Nucleoside reverse transcriptase inhibitor (NRTIs) e.g. Lamivudine (3TC), Zidovudine (AZT/ZDV), Emtricitabine (FTC), Tenofovir (TDF), Didanosine (ddI), Abacavir (ABC)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) e.g. Efavirenz and Nevirapine

Protease inhibitor (PIs) for example, Lopinavir (LPV), Ritonavir (RTV), Atazanavir (ATV), Saquinavir (SQV)

A retrovirus causes Acquired Immunodeficiency Syndrome (AIDS) by infecting CD4 cells of the immune system.

HIV attacks cells of immune system particularly CD4 cells.

T-helper cells have receptors (CD4 receptors) through which HIV attaches before it is uncoated.

HIV paves the way to other pathogenic and opportunistic infections.

Diagnosis involved doing serological rapid tests and ELISA.

Treatment involves simultaneous use of more than one drug of different classes.

What are characteristics of HIV?

What are the important viral enzymes of HIV?

What are the classes of antiretroviral drugs used in treatment of HIV&AIDS?

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