Asymptomatic primary Merkel cell polyomavirus infection among adults

Abstract

Merkel cell polyomavirus (MCV) is a recently discovered virus that causes 80% of Merkel cell carcinomas. We examined data for 564 gay/bisexual male participants >18 years of age in the Multicenter AIDS Cohort Study in Pittsburgh, Pennsylvania, USA, and found that 447 (79.3%) were MCV-antibody positive at initial enrollment. Of the 117 MCV-seronegative men, 31 subsequently seroconverted over a 4-year follow-up period, corresponding to a 6.6% annual conversion rate. MCV immunoglobulin G levels remained detectable up to 25 years after exposure. No signs, symptoms, or routine diagnostic test results were associated with MCV infection, and no correlation between HIV infection or AIDS progression and MCV infection was noted. An initial correlation between chronic hepatitis B virus infection and MCV prevalence could not be confirmed among MCV seroconverters or in studies of a second hepatitis B virus-hyperendemic cohort from Qidong, China. In adults, MCV is typically an asymptomatic, common, and commensal viral infection that initiates rare cancers after virus (rather than host cell) mutations.

Figure 1

Merkel cell polyomavirus immunoglobulin G reactivity among Multicenter AIDS Cohort Study participants, Pittsburgh, Pennsylvania, USA. A) Flowchart of test results for 564 participants and for 108 participants with initial negative tests who were available for follow-up testing. B) Combined results for initial and follow-up testing.

Figure 2

Age-dependent prevalence of Merkel cell polyomavirus antibodies among the Multicenter AIDS Cohort Study participants, Pittsburgh, Pennsylvania, USA. A small but significant linear trend for Merkel cell polyomavirus positivity with age among adult gay and bisexual men plateaued in the 35–45-year-old age group. Whiskers represent 95% confidence intervals.

Figure 3

Representative patterns of Merkel cell polyomavirus (MCV) seroconversion among participants in the Multicenter AIDS Cohort Study, Pittsburgh, Pennsylvania, USA. Most participants showed MCV immunoglobulin (Ig) M (green line) and IgG (blue line) patterns similar to patient 1 (A) (MCV IgM peak immediately preceding IgG seroconversion) or patient 2 (B) (MCV IgM and IgG are concordant). For patient 3 (C), no IgM peak was detected during MCV IgG seroconversion. Delayed MCV IgG seroconversion, as seen with patient 4 (D), could also occur 1–2 years after an initial IgM spike. The black line represents the 0.2 optical density threshold value for MCV IgG positivity. The specificity of this test is shown by MCV virus-like particle (VLP) competition (red line) and BK virus (BKV) competition (gold line), in which MCV IgG titers are measured after plasma are preincubated with VLP antigen from the respective viruses. MCV IgG reactivity is markedly reduced by MCV competition but not BKV competition.

Figure 4

Two general patterns for Merkel cell polyomavirus (McV) immunoglobulin G levels after seroconversion among participants in the Multicenter AIDS Cohort Study, Pittsburgh, Pennsylvania, USA: a gradual increase over the 25-year period (A, patient 5) or a multiyear decline during 25-year follow up (B, patient 6). Horizontal line represents the 0.2 optical density threshold value for positivity.