Viral load, clinical disease severity and cellular immune responses in primary varicella zoster virus infection in Sri Lanka.
BACKGROUND
In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied.


METHODS
We used IFNgamma ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection.


RESULTS
Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p<0.001) and were significantly higher in those over 25 years of age (P<0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNgamma ELISpot responses of patients (P<0.001, r = -0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation.


CONCLUSIONS
Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses.
Malavige
Gathsaurie Neelika
GN
MRC Human Immunology Unit, Oxford Biomedical Research Centre, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Jones
Louise
L
Kamaladasa
S D
SD
Wijewickrama
A
A
Seneviratne
S L
SL
Black
Antony P
AP
Ogg
Graham S
GS
D000328:Adult; D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D002644:Chickenpox / Q000276:immunology* / Q000821:virology*; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D008875:Middle Aged; D013188:Sri Lanka; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load; D055815:Young Adult
D017931:DNA Primers; D004279:DNA, Viral; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains