Duesberg Assignment

1 and 2) Following the advent of techniques such as Polymerase Chain Reaction (PCR), it is possible

to detect and analyse proviral DNA and viral RNA even in patients with AIDS. (Schutzbank and Smith,

1995) (Schwartz et al., 1991) (Vankerckhoven et al., 1994).

3) HIV-1 following studies has been found to be fairly species specific. In a bid to search for a suitable

nonhuman primate model system for studying HIV pathogenesis, HIV-1 was found to replicate badly

when using a macaque model (Humes et al., 2012). The study using Macaques were to investigate

the species specific amino acid sequences of the CD4+ Receptors. It was found that following infection

with HIV-1, the macaque CD4+ receptor was inefficient in mediating entry into cells. Another study

looking at species-specific co-factors essential for efficient replication, found that species-specific

genetic variations hindered the process of replication (Sherer et al., 2011). Both these studies show

good indication for species-specific hindrance for HIV-1 infection and therefore inability to go onto

cause AIDS, when using a model such as a chimpanzee.

Needle stick injuries have been well documented as causing HIV infection. Figures from the British

Journal of Anaesthesia, suggest 3 per 1000 needle stick injuries result in an HIV infection (Diprose et

al., 2000). Another good example for accidental infection is the case of the dentist David Acer.

Following an investigation by the Centre for Disease control, he was discovered to have infected

seven of his patients with HIV. Kimberly Bergalis one of his patient’s went on to develop AIDS 24

months after the initial infection. Another patient Barbara Webb now a prominent AIDS activist also

went on to develop AIDS (Cavender, 1992).

4) Infection by HIV is not the only reason for the death and loss of T-cells. There are biochemical

mechanisms in place which are capable of inducing spontaneous apoptosis in uninfected CD4+ and

CD8+ T-cells. Interaction of viral proteins such as Env with uninfected T-cell receptors such as CD4+

and the chemokine receptor CXCR4 has been found to induce apoptosis (Selliah and Finkel, 2001).

During clinical latency there is a daily viral production of 2 x 109 HIV particles, this is controlled by the

daily production of 2.6 x 109 new CD4+ cells. Lysed CD4+ cells release vast amounts of viral particles

which go on to infect more cells. It is in effect a continuing battle to produce enough T-cells to combat

the daily production of new virus. Eventually the levels of CD4+ cells simply cannot keep up and AIDS

will develop (Cann, 1997).

5) The immune system is able to cope with this initial infection with the virus, however it cannot

completely eradicate it, as it hides within non dividing memory T-cells and this acts as a reservoir.

During latency the HIV virus progressively kills off the CD4+ cells and continues to replicate within

lymph nodes due to their interaction with dendritic cells. Eventually CD4+ cells become unable to

sustain the immune system and AIDS will develop. HIV may be inactive at this point, but due to

depletion of the immune system by HIV, opportunistic infections are free to take hold of an immune

system which is essentially defenceless. The latency period is required for adequate depletion of the

immune system to allow for AIDS onset (Dimmock et al., 2007).

6) The initial immune response by interferon gamma produces flu like symptoms, CD4+ levels rise in

response to this and the virus colonises these cells, there is then a decrease in CD4+ levels during this

first infection period, after a while however the body replaces these CD4+ cells and viral numbers drop

as the immune system produces antibodies against GP120 (Flint et al., 2009). Variability in clinical

latency can be due to a number of factors including mutations in the viral proteins such as NEF. This

mutation results in the virus not being able to hide so efficiently from the immune system, resulting in

low viral numbers (Mwimanzi et al., 2011). AIDS does not progress immediately as the immune

system is able to keep the virus under control whilst CD4+ numbers are adequate.

7) HIV not only kills the CD4+ cells that are infected, cytolysis can occur in uninfected cells simply

when contact is made between these cells. This is partly due to the actions of the viral protein NEF

(Fujii et al., 1996).

Experiments conducted by Jeeninga et al (2008) to examine HIV-1 latency in actively dividing cells,

concluded that within the pathway SupT1 cell line, proviral latency was occurring. These results were

able to indicate that HIV-latency is a feature of both non-dividing cells as well as actively dividing cells.

8) HIV infection had strong connections to sexual behaviour and this varies amongst different

communities. Homosexuality is generally accepted in the United States and figures gathered in 2010

by the Centre for Disease control into the number of new HIV infections per year in the United States,

estimated that most-affected were gay white and black males (CDC, 2012). This is not the case in

many parts of Africa, where it is frowned upon and even illegal to be gay. Most of the people affected

in Africa are heterosexual. However, as committing sodomy is in some cases illegal, it is unlikely that

figures from Africa reflect or even include accurate numbers for HIV infection following homosexual

acts. High risk groups in Africa include female prostitutes and males partaking in heterosexual acts

with multiple female partners (Hunter, 1993).

The diseases associated with AIDS such as Kaposi’s sarcoma, Pneumocytosis and cytomegalovirus

are prevalent among all groups including, homosexuals, heterosexuals and intravenous drug users,

with the highest numbers being homosexuals (Lundgren et al., 1995) (Nasti et al., 2003).

In Africa endemic infectious diseases such as tuberculosis and malaria frequently infect HIV patients

and play a key role in fever, diarrhoea and malnutrition, thus resulting in “slim disease” (Anabwani and

Navario, 2005).

9) There is evidence to suggest HIV was present within humans further back than the 1980s. Using

evolutionary trees, Hillis (2000) was able to deduce a common ancestor. This date with a 95%

confidence interval was given as 1931.

The “cut theory” proposed by the virologist Crawford (2013) suggests that as early as 1900, hunters

within the Cameroon were infected when preparing infected bushmeat.

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