CCR5- and CXCR4-tropic subtype C human immunodeficiency virus type 1 isolates have a lower level of pathogenic fitness than other dominant group M subtypes: implications for the epidemic.
Human immunodeficiency virus type 1 (HIV-1) subtype C is the dominant subtype globally, due largely to the incidence of subtype C infections in sub-Saharan Africa and east Asia. We compared the relative replicative fitness (ex vivo) of the major (M) group of HIV-1 subtypes A, B, C, D, and CRF01_AE and group O isolates. To estimate pathogenic fitness, pairwise competitions were performed between CCR5-tropic (R5) or CXCR4-tropic (X4) virus isolates in peripheral blood mononuclear cells (PBMC). A general fitness order was observed among 33 HIV-1 isolates; subtype B and D HIV-1 isolates were slightly more fit than the subtype A and dramatically more fit than the 12 subtype C isolates. All group M isolates were more fit (ex vivo) than the group O isolates. To estimate ex vivo transmission fitness, a subset of primary HIV-1 isolates were examined in primary human explants from penile, cervical, and rectal tissues. Only R5 isolates and no X4 HIV-1 isolates could replicate in these tissues, whereas the spread to PM1 cells was dependent on active replication and passive virus transfer. In tissue competition experiments, subtype C isolates could compete with and, in some cases, even win over subtype A and D isolates. However, when the migratory cells from infected tissues were mixed with a susceptible cell line, the subtype C isolates were outcompeted by other subtypes, as observed in experiments with PBMC. These findings suggest that subtype C HIV-1 isolates might have equal transmission fitness but reduced pathogenic fitness relative to other group M HIV-1 isolates.
Abraha
Awet
A
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Nankya
Immaculate L
IL
Gibson
Richard
R
Demers
Korey
K
Tebit
Denis M
DM
Johnston
Elizabeth
E
Katzenstein
David
D
Siddiqui
Asna
A
Herrera
Carolina
C
Fischetti
Lucia
L
Shattock
Robin J
RJ
Arts
Eric J
EJ
D017954:Africa South of the Sahara; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D008297:Male; D010641:Phenotype; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D014779:Virus Replication
D019713:Receptors, CCR5; D019718:Receptors, CXCR4