Table 1: Studies that investigated the association of APOBEC gene variants and the course of human viral infections.

A3 family memberSeries descriptionMain findingsReference

A3B4,216 individuals from five HIV-1 natural history cohorts based in the United States of America Homozygous deletion associated with increased risk for HIV-1 infection ( ), progression to AIDS ( ), and viral set point ( )[94]

A3B724 HBV carriers and 469 healthy control subjectsAPOBEC3B deletion homozygosity was associated with mild liver fibrosis ( )
No significant association between deletion and chronic HBV infection

A3B361 Japanese subjects: 95 HIV-1-infected patients (48 nonprogressors and 47 slow progressors) and 266 controls
453 Indian subjects: 251 HIV-1-infected patients and 202 controls
No evidence of association between the APOBEC3B deletion and susceptibility to HIV infection and AIDS[96]

A3B1,124 individuals with HCC, 510 individuals with persistent HBV infection, and 826 healthy controls. All subjects were of Han Chinese ethnicityHigher frequency of the APOBEC3B deletion allele in persistent HBV carriers ( ) and HCC patients ( ) compared to controls
Presence of at least one deletion allele was associated with an increased risk for persistent HBV infection ( ) and HCC development ( )

A3B179 HBV chronic carriers and 216 healthy control subjects from the Moroccan populationNo significant difference in the frequency of deleted APOBEC3B alleles between patients with chronic hepatitis B and control subjects
Subjects carrying the Del/Del genotype displayed a trend for increased susceptibility to HBV infection compared to the wild type genotype ( )
Carriers of the APOBEC3B deletion had significantly lower viral loads than patients with the wild type genotype ( )

A3G3,073 participants enrolled in six HIV/AIDS prospective cohorts: 1,481 European Americans, 949 African Americans from five US-based cohorts, and 643 patients enrolled in the Swiss HIV cohort For African Americans, the variant allele 186R was strongly associated with a decline of CD4+ T cells ( )[99]

A3G773 white French individuals: 327 HIV-1+ (245 slow progressors; 82 rapid progressors) and 446 healthy control subjects of similar ethnic origin 29 polymorphisms with allele frequencies >1% were identified
No significant associations were found between the polymorphisms or haplotypes and disease progression

A3G136 adult HIV-infected patients from the Western Australian HIV cohort22 single nucleotide polymorphisms were identified
No significant association of these APOBEC3G genetic variants and the presence of HIV-1 hypermutation was found (although an intronic allele 6892C was marginally associated with HIV-1 hypermutation)

A3G122 Caucasian individuals exposed to HIV enrolled in prospective cohort studies in MontrealThe C40693T variant was significantly associated with an increased risk of infection ( )[102]

A3G560 North Indians: 50 HIV-1 exposed seronegative individuals, 190 HIV-1+ patients, and 320 healthy controlsNo H186R polymorphism of APOBEC3G was found among North Indians[103]

A3G250 South African women at high risk for HIV-1
subtype C infection
The H186R mutation and a 3′ extragenic mutation (rs35228531) were associated with high HIV viral loads ( and ) and decreased CD4+ T-cell counts ( and )[104]

A3G534 children perinatally exposed to HIV-1 (109 exposed uninfected and 425 HIV-1-infected), from a pediatric cohort of white-Hispanic ethnicity from ArgentinaHIV-1 perinatal transmission and progression to AIDS were not affected by APOBEC3G H186R or APOBEC3G C40693T
APOBEC3G C40693T was correlated with substitutions in Vif motifs involved in the interaction with APOBEC3G ( )

A3G400 HIV-1-infected individuals naive to drug therapy from the Brazilian populationSeven loci were analyzed: SNP −571 (rs5757463); −199 (rs34550797); −90 (rs5750743); 119 (rs5757465); 186 (rs8177832); 197 (rs3736685); 199 (rs2294367)
For the SNP −571, heterozygous (C/G) and homozygous (G/G) individuals had lower CD4+ T-cell counts compared to homozygous (C/C) individuals ( )

A3G93 perinatally infected children with white-Hispanic ethnicity, from an Argentinian pediatric cohortThe APOBEC3G H186R and APOBEC3G C40693T variants were not associated with different levels of HIV-1 editing [107]

A3G1,049 HIV-1-infected children from the Pediatric AIDS Clinical Trials Group (PACTG) protocols P152 and P300 (60% non-Hispanic black, 26% Hispanic, 13% non-Hispanic white, and 1% other or unknown race/ethnicity)APOBEC3G H186R homozygous G/G genotype was associated with faster HIV-1 disease progression ( ) and central nervous system (CNS) impairment ( )
APOBEC3G F119F-C allele was associated with protection against disease progression and CNS impairment in both additive and dominant models ( and , resp.) and CNS impairment ( and , resp.)

A3G179 HBV chronic carriers and 216 healthy control subjects from the Moroccan populationNo significant difference in the frequencies of APOBEC3G H186R genotype between patients with chronic hepatitis B and control subjects[98]

A3H70 Italian HIV-exposed seronegative individuals and their HIV-1-infected sexual partnersThe APOBEC3H haplotype I was found in a higher frequency in the exposed seronegative compared to the HIV+ individuals ( ), suggesting a protection from sexually transmitted HIV-1 infection[109]

A3H96 recently HIV-1-infected treatment-naïve adults 68 SNPs were analyzed
Homozygous carriers of an APOBEC3H risk haplotype (A3Hrh) had lower GA→AA (A3F) sequence editing on proviral HIV-1 vif sequence ( ) and lower HIV-1 RNA levels ( )