Biology Reference
In-Depth Information
coreceptor usage ( Isaka et al., 1999). Importantly, analysis of chimeric viruses
has revealed that changes in the V3 loop can convert a nonsyncytium inducing
(NSI), slowly replicating virus into a syncytium inducing (SI ), rapidly repli-
cating virus (Shioda et al., 1992).
CONCLUSION
Expanded analysis of the molecular biology of HIV has been the key to under-
standing the mechanisms by which this virus persists in the host and causes
AIDS, and to developing e¨ective antiretroviral strategies. Application of pow-
erful molecular biology tools has allowed researchers to obtain fundamental
results on many aspects of HIV biology in vitro (i.e., in cell-free and tissue
culture systems) and in vivo (i.e., directly in samples from the susceptible host).
Importantly, knowledge of the molecular mechanisms in each step of the virus
life cycle has provided an essential basis for discovering new antiviral com-
pounds. Otherwise, a ®rm understanding of the relevant features of both the
HIV turnover in vivo and the intrahost HIV evolution is crucial for developing
e¨ective anti-HIV strategies. Indeed, the HIV biology poses several challenges
to the development of these strategies. In particular, sequence variation result-
ing from errors of the viral RT and recombination renders HIV an elusive tar-
get for both antiviral compounds and vaccines. In this context, novel diagnos-
tic molecular tools to control development of viral resistance to the di¨erent
classes of antivirals and new e¨ective therapeutic approaches, including genetic
and immunologic strategies, could be the key to inhibiting HIV replication in
the future.
REFERENCES
Bagnarelli P, Valenza A, Menzo S, Manzin A, Scalise G, Varaldo PE, Clementi M. 1994. Dynamics
of molecular parameters of human immunode®ciency virus type 1 activity in vivo. J Virol 68:
2495±2502.
Bagnarelli P, Valenza A, Menzo S, Sampaolesi R, Varaldo PE, Butini L, Montroni M, Perno CF,
Aquaro S, Mathez D, Leibowitch J, Balotta C, Clementi M. 1996. Dynamics and modulation of
human immunode®ciency virus type 1 transcripts in vitro and in vivo. J Virol 70: 7603±7613.
Bagnarelli P, Mazzola F, Menzo S, Montroni M, Butini L, Clementi M. 1999. Host-speci®c mod-
ulation of the selective constraints driving human immunode®ciency virus type 1 env gene evo-
lution. J Virol 73: 3764±3777.
Berkhout B, van Hemert, FJ. 1994. The unusual nucleotide content of the HIV RNA genome re-
sults in a biased amino acid composition of HIV proteins. Nucleic Acid Res 9: 1705±1711.
Dougherty JP, Temin HM. 1988. Determination of the rate of base-pair substitution and insertion
mutations in retrovirus replication. J Virol 62: 2817±2822.
Furtado MR, Kingsley LA, Wolinsky SM. 1995. Changes in the viral mRNA expression pattern
correlate with a rapid rate of CD4
T cell number decline in human immunode®ciency virus
type 1-infected individuals. J Virol 69: 2092±2100.
