Defective virus
Virus which has lost a gene that is essential for replication and
can, therefore, only undergo productive infection if the cell that is harbouring
the virus is superinfected with a helper virus that can supply the
function of the lost gene.
Many oncogenic retroviruses are defective.
Endogenous reteroviral sequences
Defective retroviruses which integrate into the host genome and are
passed down from generation to generation. Two percent of the human genome
is made up of endogenous retroviral sequences.
Genome organization The virus has a diploid genome (2 copies of RNA genome per virus particle). The genome codes for at least three genes: gag, pol and env.
LTR -Long terminal repeat - is a regulatory sequence at each end of
the genome.
Their presence allows integration into the host chromosome and controls
gene expression
onc - (see oncogenes)
Viruses of the Oncovirinae subfamily contain an extra gene termed, 'onc'. These genes are called oncogenes because their expression in the virus infected cell is associated with tumour production. These genes were originally acquired from the host cell itself. The cellular gene was picked up during integration of the virus genome into the host DNA, way back in evolution. Most oncogenes code for proteins with growth promoting properties and their expression can lead to uncontrolled proliferation of the infected cell and tumour development.
Human T-Cell Lymphotrophic Viruses, belong to the sub-family Oncovirinae.
Clinical features
1. T-cell leukaemia/lymphoma. Aggressive tumour of CD4 cells
which infiltrates skin and brain. Tumours are only produced after a prolonged
latent period. The virus does not contain an oncogene and it is believed
that the malignant change is the result of interruption and disregulation
of host DNA, by viral genome insertion. Less than 1% of HTLV 1 infected
individuals develop this malignancy.
2. Tropical spastic paraparesis. Aggressive non-demyelinating spastic paraparesis.
Epidemiology
Seroprevalence is high in South West Japan, the Caribbean and parts of West
Africa. In high incidence areas up to 10% of adults may be infected. The
seroprevalence increases with age and family clustering of infection is common.
Spread occurs through blood transfusion and sexual intercourse. Mother to
child transmission through breast feeding has also been shown.
Laboratory Diagnosis
HTLV 1 specific antibody, ELISA.
The virus shares extensive nucleic acid homology with HTLV 1. It was first isolated from a patient with hairy cell leukaemia, but no specific pathology has been attributed to it.
Human Immunodeficiency Viruses
At this time an infectious aetiology was suspected especially when it was perceived the disease could be transmitted by blood transfusions and blood products. (Haemophiliacs)
In 1983, a new retrovirus termed LAV (now called HIV 1) was isolated from the T-cells of a patient with persistent generalised lymphadenopathy.
In 1986, a second closely related virus, termed HIV 2 was isolated from a patient from West Africa with acquired immunodeficiency syndrome, AIDS.
Currently, about 14 million people are believed to be infected, world-wide; nine million of these are in Africa (see figure 2). HIV1 is the major cause of the AIDS pandemic; HIV2 is of lower virulence and infection has largely remained confined to West Africa.
Origin
AIDS appears to be a new disease. The origin of the virus is obscure but
it is probable that infection arose in Africa. Retrospective screening of
stored sera has shown that the earliest known infection occurred in Kinshasa,
Zaire, in 1959.
HIV is believed to have evolved from related viruses that infect African
monkeys, namely the simian immunodeficiency viruses (SIV) (which cause
a similar disease to AIDS in monkeys). HIV 2 is more closely related to SIV
than HIV 1. It is not known how the original transfer of virus from monkey
to man took place. These viruses mutate readily which explains the rapid
subsequent divergence.(figure 4)
Spread(figure 3)
Epidemiology - South Africa
HIV was introduced into South Africa from two sources:
a) Into the homo-sexual community - from North America and Europe,and
b) into the hetero-sexual community - from north of our borders by truck
drivers, returning exiles, migrant labourers.
A survey, conducted in October/November 1993, of women attending ante natal clinics in different parts of the country has shown that the prevalence of HIV infection varies from 1.33% in the Cape to 9.62% in KwaZulu/Natal.
Transmission
Infection is transmitted in a manner identical to that of hepatitis B.
1.) Blood products
2.) Organ transplants
3.) Sexual intercourse
Both homosexual and hetero-sexual exposure
Increased risk of transmission if partners have other sexually transmitted
diseases
4.) Vertical Transmission
10-40% of babies born of HIV-infected mothers will be infected.
Primary infection
About 90% of patients develop a flu-like illness which co-incides with
seroconversion, between 2 and 4 weeks post exposure. Symptoms include, fever,
night sweats, sore throat, lymphadenopathy, diarrhoea. The illness is self
limiting.
Asymptomatic phase
Of variable duration, from 2 to 10 years. Patients are clinically well, but
infectious.
Prodromal phase
This period is heralded by the insidious onset of a variety of prodromal
disorders, including: weight loss, fever, persistant lymphadenopathy, oral
candidiasis and diarrhoea. These symptoms precede the progression to AIDS.
Acquired Immunodeficiency Syndrome (AIDS)
Kaposi sarcoma - is a tumour of endothelial cells. Prior to the AIDS epidemic, this tumuor was rare and only found in middle aged African and Mediterranean Jewish men, in whom it was an indolent condition. AIDS patients develop a disseminated highly aggressive form of the disease.
Paediatric Infection
Following infection in the perinatal period, babies may develop a progressive
illness in the first few months of life (No latent period). Clinical features
include: Failure to thrive, diarrhoea, lymphadenopathy, susceptibility to
opportunistic infections hepato-splenomegaly, lymphoid interstitial pneumonia
and parotitis.
HIV infects CD4 cells
Disseminated infection
Clearance of most virus
Cell tropism: CD4+ T cells, Macrophages
Infection of precursor cells and destruction of microenvironment
Impairment of CD4 cell function
Serology
IgG develops 4-6 weeks post exposure and remains detectable for life. Its
presence in serum therefore indicates infection.
Exception: Uninfected infants of HIV positive mothers
Direct detection of virus
p24 antigen ELISA
culture from PBMC's
PCR
There is no effective vaccine available for HIV. Attempts have been made
to develop a vaccine, using:
A major difficulty is the fact that neutralizing antibody in the serum does
not protect the host from infection with HIV: Possible reasons for this
include:
Illustrations and layout by Linda Stannard, 1999 ©