391Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA-damage
response, and RNA splicing were identifi ed as important modulators of early-stage
HIV-1 infection. Additionally, over 40 new factors were shown to specifi cally infl u-
ence the initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal
regulatory proteins, modulators of posttranslational modifi cation, and nucleic acid-
binding proteins. Finally, 15 proteins with diverse functional roles, including nuclear
transport, prostaglandin synthesis, ubiquitination, and transcription, were found to
infl uence nuclear import or viral DNA integration. Altogether, there are 295 host cell
factors that likely act in concert to facilitate the early steps of HIV-1 infection. Although
it is known for a long time that HIV hijacks our cellular proteins to complete its life
cycle, this study now lays out its fl ight plan. These fi ndings may yield novel therapeu-
tic targets for HIV.
Genetic Basis of Human Body’s Resistance Against HIV
The body’s fi rst response to HIV strongly infl uences the rate at which the virus will
destroy the immune system. Shortly after infection, HIV levels rise steeply, but then
the immune system and other antiviral factors produced by cells drive down the viral
load and establish a “set point.” The lower the set point, the longer the immune sys-
tem can function effectively. These set points vary widely in individuals.
Understanding why some people establish and maintain effective control of HIV-1
and others do not is a priority in the effort to develop new treatments for HIV/
AIDS. Using a whole-genome association strategy, scientists have identifi ed poly-
morphisms that explain nearly 15 % of the variation among individuals in viral load
during the asymptomatic set point period of infection (Fellay et al. 2007 ). One of
these is found within an endogenous retroviral element and is associated with major
histocompatibility allele HLA-B*5701, while a second is located near the HLA-C
gene. An additional analysis of the time to HIV disease progression implicated a third
locus encoding a RNA polymerase subunit. These fi ndings emphasize the importance
of studying human genetic variation as a guide to combating infectious agents. The
genetic polymorphisms could form the basis of more effective vaccines and antiviral
agents against HIV. However, this study largely focused on Caucasians and the
results need to be replicated in the context of a different genetic background.
Pathogenesis of AIDS
It is important to understand the molecular mechanism by which the HIV virus
infects, or integrates, healthy cells. The integration of retroviral DNA by the viral
integrase into the host genome occurs via assembled pre-integration complexes. By
using Fluorescence that the Integrase holds the two ends of the viral DNA together
prior to integration as shown by resonance energy transfer. Once inside the cell, the
two viral DNA ends are fused by the integrase to the cell’s chromosome. The inte-
grated viral DNA allows virus replication. If the two ends of the viral DNA do not
Personalized Management of Viral Infections