HIV-1 recombinants with multiple parental strains in low-prevalence, remote regions of Cameroon: evolutionary relics?
BACKGROUND
The HIV pandemic disseminated globally from Central West Africa, beginning in the second half of the twentieth century. To elucidate the virologic origins of the pandemic, a cross-sectional study was conducted of the genetic diversity of HIV-1 strains in villagers in 14 remote locations in Cameroon and in hospitalized and STI patients. DNA extracted from PBMC was PCR amplified from HIV(+) subjects. Partial pol amplicons (N = 164) and nearly full virus genomes (N = 78) were sequenced. Among the 3956 rural villagers studied, the prevalence of HIV infection was 4.9%; among the hospitalized and clinic patients, it was 8.6%.


RESULTS
Virus genotypes fell into two distinctive groups. A majority of the genotyped strains (109/164) were the circulating recombinant form (CRF) known to be endemic in West Africa and Central West Africa, CRF02_AG. The second most common genetic form (9/164) was the recently described CRF22_01A1, and the rest were a collection of 4 different subtypes (A2, D, F2, G) and 6 different CRFs (-01, -11, -13, -18, -25, -37). Remarkably, 10.4% of HIV-1 genomes detected (17/164) were heretofore undescribed unique recombinant forms (URF) present in only a single person. Nearly full genome sequencing was completed for 78 of the viruses of interest. HIV genetic diversity was commonplace in rural villages: 12 villages each had at least one newly detected URF, and 9 villages had two or more.


CONCLUSIONS
These results show that while CRF02_AG dominated the HIV strains in the rural villages, the remainder of the viruses had tremendous genetic diversity. Between the trans-species transmission of SIVcpz and the dispersal of pandemic HIV-1, there was a time when we hypothesize that nascent HIV-1 was spreading, but only to a limited extent, recombining with other local HIV-1, creating a large variety of recombinants. When one of those recombinants began to spread widely (i.e. became epidemic), it was recognized as a subtype. We hypothesize that the viruses in these remote Cameroon villages may represent that pre-epidemic stage of viral evolution.
Carr
Jean K
JK
Institute of Human Virology, Univ, of Maryland School of Medicine, Baltimore, MD, USA. jecarr@ihv.umaryland.edu
Wolfe
Nathan D
ND
Torimiro
Judith N
JN
Tamoufe
Ubald
U
Mpoudi-Ngole
E
E
Eyzaguirre
Lindsay
L
Birx
Deborah L
DL
McCutchan
Francine E
FE
Burke
Donald S
DS
D000328:Adult; D002163:Cameroon; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D019143:Evolution, Molecular; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006761:Hospitals; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012424:Rural Population; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D004279:DNA, Viral; D054302:pol Gene Products, Human Immunodeficiency Virus