Dengue Literature Review

DENV-1

4 min read

DENV-1

Overview

DENV-1 is one of the four dengue virus serotypes. It was the first to be introduced into Cuba (1977 epidemic), making it the initial sensitising serotype for Cuban adults who later experienced DENV-2 secondary infections in 1981 and DENV-4 tertiary/quaternary infections in 2006. Globally, DENV-1 circulates throughout the dengue-endemic tropics and is associated with both dengue fever and, in secondary infections, severe dengue.

Key Points from Literature

  • The Cuban epidemic sequence — DENV-1 (1977) → DENV-2 (1981) → DENV-3 (2001) → DENV-4 (2006) — is a key natural experiment demonstrating how prior infection history shapes disease severity. Most Cuban adults infected in 2006 (the Garcia2009/2010 cohort) were experiencing secondary, tertiary, or quaternary infections, with DENV-1 typically the original sensitising infection (see Guzman2016 - Dengue Infection).
  • The DENV1→DENV2 secondary sequence is the classic severe dengue pairing: in Santiago de Cuba (1997), individuals experiencing secondary DENV-2 after prior DENV-1 had an overt-to-subclinical disease ratio of nearly 1:1, whereas primary DENV-2 infections were predominantly subclinical (see Guzman2016 - Dengue Infection).
  • By contrast, in Rayong, Thailand (1980), secondary DENV-1 infections (after prior DENV infection) comprised 37.5% of all secondary infections yet produced no severe disease — demonstrating that the DENV1→DHF association is sequence- and context-dependent, not absolute (see Guzman2016 - Dengue Infection).
  • A broadly cross-neutralising antibody class has been identified that targets quaternary epitopes at the DI-DII hinge of the E protein and provides pan-DENV neutralisation; whether such antibodies are preferentially selected during secondary DENV-1 infections is unknown.

Singapore 2005 Outbreak

  • In the October–November 2005 dengue outbreak in Singapore, DEN-1 was the dominant circulating serotype: 20 of 27 virologically typed patients (74%) had DEN-1 isolated from serum. DEN-3 was the minor circulating serotype (6/27, 22%), with DEN-4 in 1 patient (see Seet2007 - Post-Infectious Fatigue Syndrome in Dengue).
  • This places Singapore in a different serotype-epidemiology context than Cuba in the same era (DENV-4 dominant in Cuba 2006; DENV-1 the initial sensitising serotype from 1977 onwards). In Singapore, DEN-1 remained the primary circulating serotype in 2005, suggesting it had not yet been displaced by other serotypes as occurred in the Cuban sequence.

DENV-1 NS1 levels and primary viraemia (Bhatt2020)

Bhatt2020 - Dengue Pathogenesis Review notes that DENV-1 primary infection is associated with higher circulating NS1 levels and higher primary viraemia than DENV-2 primary infection (see NS1 Protein). By contrast, DENV-2 secondary infection produces the highest overall viraemia across infection sequences. This suggests that serotype-specific differences in NS1 secretion or replication efficiency contribute to the variation in NS1 titre observed across clinical cohorts — with important implications for the clinical utility of NS1 as a severity biomarker (which correlates with severity specifically in secondary infection, see Viraemia).

Contradictions & Debates

  • The severity of secondary DENV-1 infection varies dramatically by geographic context (severe in Santiago de Cuba 1997; not severe in Thailand 1980), suggesting intrinsic serotype virulence is less important than host immune history, viral genotype, and local vector competence. The paper frames DENVs as “conditionally virulent” rather than intrinsically so.

Sources

Graph View

Backlinks