ID 112983
Title Alternative
Strategy of HIV‐1 for survival : mutation, adaptation and evolution
Author
Keywords
HIV‐1
adaptation
macaque-tropic HIV‐1
pathogenesis
replication control
Content Type
Journal Article
Description
Viruses are the smallest self-replicating organisms in nature. Without a metabolic system of their own, they survive in their hosts by ably utilizing host’s cellular machinery. To this end, viruses must continue to mutate and adapt in host’s varying environments. This adaptation ability is a fundamental property of viruses, closely linking to their survival. Understanding molecular bases for viral mutation and adaptation would certainly lead to the establishment of novel strategies against viruses.
HIV‐1 exhibits a narrow host range, and disease-inducing infections are observed only in human population. The important question “Why and how does HIV‐1 cause disease only in human?” must be demonstratively solved. To address this issue, HIV‐1infection models for AIDS are essential. Since valid animal models for this purpose have not been established yet, we now aim at constructing a novel class of HIV‐1(HIV‐1rmt)that infects experimental macaques and causes AIDS. Recent studies suggested that HIV‐1 emerged in human population following repeated species transmission/adaptation to new hosts of different SIVs from various hosts. Generation of HIV‐1rmt could be considered as an opposite process to HIV‐1 emergence, i.e., adapting human-specific HIV‐1to replicate in new host macaques. HIV‐1rmt is a good model virus to determine functional and structural changes for survival in new hosts. To overcome species barrier, we modified HIV‐1genome by using two techniques : virus adaption and assisted evolution. Finally, we successfully constructed HIV‐1rmt clones which can antagonize all intrinsic restriction factors in macaque cells. Moreover, virological analyses of growth-enhancing mutations appeared in adaptation processes of the prototype HIV‐1rmt led to the identification of novel genomic regulatory elements for Vif expression. Our experimental system using HIV‐1rmt and macaque cells provides pivotal information on molecular bases for species-specific HIV‐1 replication, and would thus contribute to understanding the HIV‐1pathogenesis.
Journal Title
Shikoku Acta Medica
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
74
Issue
5-6
Start Page
163
End Page
170
Sort Key
163
Published Date
2018-12-25
FullText File
language
jpn
TextVersion
Publisher
departments
Medical Sciences