1. 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

2. 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.

3. Reference List
ANABWANI, G. & NAVARIO, P. 2005. Nutrition and HIV/AIDS in Sub-Saharan Africa: an overview.
Nutrition, 21, 96-99.
CANN, A. 1997. Principles of molecular virology, London, Academic Press.
CAVENDER, J. W. 1992. AIDS in the health care setting: the congressional response to the Kimberly
Bergalis case. Georgia law review (Athens, Ga. : 1966), 26, 539-99.
CDC 2012. New HIV infections in the United States. In: CONTROL, C. F. D. (ed.). Atlanta: Centers for
Disease Control and Prevention.
CRAWFORD, D. H. 2013. Virus hunt : the search for the origin of HIV, Oxford, Oxford University
Press.
DIMMOCK, N. J., EASTON, A. J., LEPPARD, K. & NETLIBRARY, I. 2007. Introduction to modern
virology, Malden, MA, Blackwell Publishing.
DIPROSE, P., DEAKIN, C. D. & SMEDLEY, J. 2000. Ignorance of post-exposure prophylaxis
guidelines following HIV needlestick injury may increase the risk of seroconversion. British
Journal of Anaesthesia, 84, 767-770.
FLINT, S. J., ENQUIST, L. W., RACANIELLO, V. R. & SKALKA, A. M. 2009. Principles of Virology,
Washington, D. C, ASM Press.
FUJII, Y., OTAKE, K., TASHIRO, M. & ADACHI, A. 1996. In vitro cytocidal effects of human
immunodeficiency virus type 1 Nef on unprimed human CD4(+) T cells without MHC
restriction. Journal of General Virology, 77, 2943-2951.
HILLIS, D. M. 2000. Aids - Origins of HIV. Science, 288, 1757-+.
HUMES, D., EMERY, S., LAWS, E. & OVERBAUGH, J. 2012. A Species-Specific Amino Acid
Difference in the Macaque CD4 Receptor Restricts Replication by Global Circulating HIV-1
Variants Representing Viruses from Recent Infection. Journal of Virology, 86, 12472-12483.
HUNTER, D. J. 1993. Aids in sub-saharan africa - the epidemiology of heterosexual transmission and
the prospects for prevention. Epidemiology, 4, 63-72.
JEENINGA, R. E., WESTERHOUT, E. M., VAN GERVEN, M. L. & BERKHOUT, B. 2008. HIV-1
latency in actively dividing human T cell lines. Retrovirology, 5.
LUNDGREN, J. D., BARTON, S. E., LAZZARIN, A., DANNER, S., GOEBEL, F. D., PEHRSON, P.,
MULCAHY, F., KOSMIDIS, J., PEDERSEN, C. & PHILLIPS, A. N. 1995. Factors Associated
with the Development of Pneumocystis carinii Pneumonia in 5,025 European Patients with
AIDS. Clinical Infectious Disease, 21, 106-113.
MWIMANZI, P., HASAN, Z., HASSAN, R., SUZU, S., TAKIGUCHI, M. & UENO, T. 2011. Effects of
naturally-arising HIV Nef mutations on cytotoxic T lymphocyte recognition and Nef's
functionality in primary macrophages. Retrovirology, 8.
NASTI, G. Y., BALLARDINI, G., STOPPINI, L., DI PERRI, G., MENA, M., TAVIO, M., VACCHER, E.,
MONFORTE, A. D. A. & TIRELLI, U. 2003. AIDS-Related Kaposi’s Sarcoma: Evaluation of
Potential New Prognostic Factors and Assessment of the AIDS Clinical Trial Group Staging

4. System in the Haart Era—the Italian Cooperative Group on AIDS and Tumors and the Italian
Cohort of Patients Naive From Antiretrovirals Journal of Clinical Oncology, 21, 2876-2882.
SCHUTZBANK, T. E. & SMITH, J. 1995. Detection of human-immunodeficiency-virus type-1 proviral
dna by pcr using an electrochemiluminescence-tagged probe. Journal of Clinical Microbiology,
33, 2036-2041.
SCHWARTZ, H. E., ULFELDER, K., SUNZERI, F. J., BUSCH, M. P. & BROWNLEE, R. G. 1991.
Analysis of dna restriction fragments and polymerase chain-reaction products towards
detection of the aids (HIV-1) virus in blood. Journal of Chromatography, 559, 267-283.
SELLIAH, N. & FINKEL, T. H. 2001. Biochemical mechanisms of HIV induced T cell apoptosis. Cell
Death and Differentiation, 8, 127-136.
SHERER, N. M., SWANSON, C. M., HUE, S., ROBERTS, R. G., BERGERON, J. R. C. & MALIM, M.
H. 2011. Evolution of a Species-Specific Determinant within Human CRM1 that Regulates the
Post-transcriptional Phases of HIV-1 Replication. Plos Pathogens, 7.
VANKERCKHOVEN, I., FRANSEN, K., PEETERS, M., DEBEENHOUWER, H., PIOT, P. &
VANDERGROEN, G. 1994. Quantification of human-immunodeficiency-virus in plasma by rna
pcr, viral culture, and p24 antigen-detection. Journal of Clinical Microbiology, 32, 1669-1673.