Infection by Human Immunodeficiency Virus-1 
(HIV-1) is modulated by the interaction of host cell, 
viral proteins, and environmental stimuli. Critically 
involved cellular factors are apolipoprotein B 
mRNA-editing enzyme-catalytic, polypeptide-like 3 
protein family (APOBEC3), tetherin, and SAM and 
HD domain-containing protein 1 (SAMHD1). The 
functions of these restriction factors are overcome 
by viral mediators that include Viral Infectivity 
Factor (VIF) for APOBEC3, viral protein U (vpU) 
for tetherin, and Vpx (in HIV-2) for SAMHD1. In 
addition, DNA damage, the most common 
environmental stimulus, influences the multiple 
steps of the viral infection. Notably, DNA repair 
proteins play critical roles in the integration steps of 
viral DNA. The activated DNA damage response by 
viral infection leads to apoptotic cell death and 
prevents the viral propagation, suggesting that it is 
an intrinsic viral restriction mechanism. In contrast,  
the DNA damage responses can increases the 
frequency of viral infection when the integrase 
activity is defective or inhibited by integrase 
inhibitors, implying that DNA damage and its  cellular response function like dual sides of the 
same coin. In this review, we first summarize our 
current understanding of the restriction factors, and 
then focus on the roles of HIV-1-associated DNA 
damage response on the transduction of viral DNA. 
In particular, the functional association of viral 
integration with the DNA repair pathways will be 
discussed.