Biology 103 - Microbes and You

Lecture 15 Outline

AIDS - The Basics (latent viruses; herpes, shingles)



Images

Worldwide incidence of HIV infection

Death rates of US 25-44 year olds

Micrograph of Herpes virus

Herpes virus movement in nerves

HIV drug targets

HIV reports in US in 1997 by state

Binding of HIV to CD4 helper T-cell lymphocyte

Life cycle and drug targets for HIV

HIV life cycle

Map of worldwide HIV infection rates

HSV1 lesions

Chicken pox lesion

Provirus cycle for latent viruses

Retrovirus life cycle

Shingles lesions




Chicken pox
chicken pox called Varicella-zoster is caused by a herpes virus
it contains linear dsDNA and is enveloped
initial infection with the chicken pox virus causes the classic childhood disease with characteristic rash
the virus then moves down nerves from the skin and into the dorsal root ganglia cells
there the virus remains in a latent state
during this latent state, the viral genome exists as an independent self-replicating episome (or plasmid, a circle of DNA) in the cell nucleus
it can remain in this latent state for decades
the virus can then be reactivated or induced when the person is under stress, such as aging or chemotherapy
when induced, the virus moves back down the nerves to the skin and causes a rash
the rash lasts for weeks and is painful due to neuralgia (nerve pain)
this second infection is called shingles or zoster
thus, the virus first goes through the viral lytic cycle during the initial infection
and then goes through the lysogenic cycle, including a latent phase and induction to reinitiate a lytic cycle
chicken pox occurs in children with 3 million cases per yr in the US
90% of 12 year olds have had the disease
10-20% will later develop zoster
a live attenuated virus vaccine is now available

Herpes viruses
the other herpes viruses have life cycles similar to that of the chicken pox virus
two major types of herpes virus cause chronic recurrent infections:
HSV1 - generally considered the oral herpes virus can also occur in the eye and other body parts
it is the causative agent of cold sores and fever blisters
50-80% of US population is infected but only 10-20% get outbreaks of lesions
most people are infected as infants as the virus can be transmitted through casual contact
HSV2 - generally considered the genital and anal form of herpes but can occur in other body parts
this type is much more virulent than HSV1
1 of 6 US citizens are infected with genital herpes
the outbreaks of lesions generally occur annually
the herpes virus can be shed from the body even when lesions are not present
once the herpes virus enters the skin or mucosal membranes it migrates to the central nervous system and thus escapes the immune system
there the virus enters a latent phase by forming an episome in the nucleus of the host cell
the virus can later be induced by stress, UV light, hormones or injury
when induced, the virus moves down the nerve cells to again cause skin lesions

Other herpes viruses
cytomegalovirus - common in the population, only causing disease in immunocomprimised individuals
Epstein-Barr virus - over 90% of US population infected for life, may be a causative agent in cancers and chronic fatigue syndrome (the Yuppie flu)
Human Herpes Virus 6 - HHV6, 100% of US population infected, causative agent of Roseola infantum, a mild disease in infants causing rash and fever
HHV 8 - causative agent in Kaposi's sarcoma, a cancer generally only seen in immunocomprimised individuals

HIV and AIDS
human immunodeficiency virus (HIV) kills off the immune system leading to acquired immune deficiency syndrome (AIDS)
initial infection caused by intimate (sexual) contact or through contact with blood or semen
the first stage of HIV infection gives mild flu symptoms
no HIV antibodies detected in the blood
a person recently infected would test HIV negative although they are in fact infected and can transmit the disease
after a month or more the next phase ensues - seroconversion
here HIV has spread to the lymph tissue and caused serious infection
antibodies against the HIV virus can be detected in the blood and the person is HIV positive
the virus then enters a latent period
during this time the viral genome becomes integrated into the host chromosome
there the viral DNA sequences are reproduced along with the host cell genome
this latent period may last a decade or more
during this time the virus attacks white blood cells destroying the immune system
when lymphocyte titers (amount in blood) are low enough the patient is considered to have AIDS
virus can be detected in the blood and T-cell helper lymphocytes are lost
the final phase of infection is the end stage
no immune system is present and opportunistic infections eventually kill the patient

More on HIV and AIDS
the life cycle of HIV is different than most viruses
HIV is in a class of viruses called retroviruses
these viruses contain RNA
when they enter a cell, they transcribe their RNA into DNA
it is this DNA copy that integrates into the host cell genome becoming what is known as a provirus
conversion of RNA to DNA is opposed to the central dogma of molecular biology
the virus supplies the special enzyme called reverse transcriptase
the virus also contains an enzyme called integrase that helps the viral DNA copy to integrate into the host cell genome
the virus also contains proteases that cut protein polymers in specific places and modifying the translated viral proteins into a proper form for progeny virus assembly
HIV has surface proteins that specifically bind (lock and key) to surface receptors on CD4 helper T-cell lymphocytes
if you remember, helper T-cells bind to macrophages that are activated and displaying invader antigens on their surfaces and then alert the B lymphocytes of the invasion
these cells are obviously critical to proper immune system functions
by killing these cells, HIV renders the person susceptible to many diseases that a healthy immune system would fight off

AIDS and drugs
early in AIDS these opportunistic infections are common:
thrush - a fungal (Candida) infection
shingles and herpes outbreaks
oral hairy leukoplakia and thrombocytopenic purpura
later in AIDS these opportunistic infections are common and often deadly:
rare types of pneumonia
tuberculosis
Kaposi's sarcomas
toxoplasmosis, cryptococcosis (soil fungi), MAC (from bird droppings), cytomegalovirus, cryptosporidosis
HIV drugs tend to focus on biochemical functions and enzymes that are unique to the retroviruses
integrase, reverse transcriptase, and proteases are likely drug targets
AZT and ddI are reverse transcriptase inhibitors
protease inhibitors have also been recently approved
vaccines tend to focus on the binding of HIV to the CD4 cell surface receptor
the problem with HIV vaccines is that the virus mutates easily and many variants exist
the best way to avoid HIV and herpes is to avoid sexual contact
condoms only provide some protection from the virus
only abstinence from sexual intercourse, refusal to use illicit drugs delivered by used needles, and testing of blood transfusion products can assure that you will not get infected with deadly HIV



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