Picornavectors. Viruses That Spread Bacteria

Rhinoviruses (RVs) cause more infections than any other pathogen, and the reason for their success is multifactorial. From a molecular perspective, RVs replicate rapidly, inhibit host interferon responses, and mutate quickly (one mutation per 10⁴ bases, or about one mutation per virus) to adapt to local host conditions (1). These properties are shared with other picornaviruses. RVs are distinct in more than 160 types, which is an effective strategy to circumvent neutralizing antibodies. Furthermore, there are at least 20 different RV types that circulate in any given community (2), so chances are good that individuals will be susceptible to at least one of the current circulating viruses. Furthermore, as the seasons change, so do the prevalent RVs. RV infections also induce behaviors such as rhinorrhea, sneezing, and coughing that lead to transmission. In this issue of the Journal, Karppinen and colleagues (pp. 1172–1180) show that RV infections also promote spread of Streptococcus pneumoniae (3). These data suggest we might think of these viruses as very small vectors; in other words, picornavectors.

To describe the effect of RV infection on acquisition and transmission of pneumococci, Karppinen and colleagues studied 29 families with at least two children. When a respiratory illness was recognized, family members provided daily symptom diaries together with twice-weekly swabs to enable tracking of the spread of both RVs and pneumococci. Molecular viral diagnostics were used to analyze the RV types, and the bacteria were analyzed by antigen detection and by culture. A subset of pneumococcal isolates was sequenced to determine whether the isolates from within a family were likely to represent transmission. Rates of pneumococcal acquisition from the community or from the family were calculated for adults and for children. The main findings were that RV infection increased the rate of pneumococcal acquisition in children from the community (4.3-fold increase), and that the effects were even greater on pneumococcal acquisition from the family (14.8-fold increase). The authors conclude that RV infections within families facilitates both community acquisition and within-family transmission of S. pneumoniae.

There are a few limitations to the study findings that were acknowledged by the authors. Nasal swabs were obtained at home by parents, and it is possible this method underestimates bacterial colonization from other airway locations (4). In addition, the concept that viral infections could promote acquisition of pneumococcal colonization was first introduced by transmission studies conducted in the 1970s (5) and reaffirmed by more recent studies (6, 7). However, the current study adds new information through the use of frequent sampling together with molecular methods to type both the viruses and the bacteria, and convincingly proves these concepts.

Still, it remains to be determined how RV infections lead to new acquisition of pneumococcal colonization. In some cases, the pneumococci colonization may preexist in different parts of the airway (e.g., adenoidal tissue), and RV infections may facilitate the expression of pneumococcus in the nose. Furthermore, are the bacteria spread by the same mechanisms (aerosols and contact with fomites) that lead to viral transmission? Also, are viruses and bacteria transmitted and acquired at the same time, or in a stepwise process? Answers to these questions may provide insights into interventions to interrupt acquisition and spread of pneumococcal colonization.

Children are major vectors for infectious diseases, including viral respiratory illnesses such as influenza (8) and RV (9). In contrast, casual contact between adults is an inefficient way to spread viruses. For example, Peltola and colleagues studied transmission of RVs within families and found that young children were more likely to transmit the infection to adults than vice versa (9). In their current study, acquisition of pneumococcus was more likely to occur in families with many children, or in children who attended day care. Thus, children are most likely to transmit RV infections, and also are more likely to spread colonization with S. pneumoniae. For adults, the prevalence of S. pneumoniae and acquisition rates in adults were both quite low. The reasons for the age-related differences in pathogen transmission are likely to be multifactorial, and include better hygiene and mature innate and adaptive immune responses to both bacteria and viruses.

What are the implications of RV infections facilitating the spread of S. pneumoniae? Could this be of mutual benefit for the virus and the bacteria? One mechanism to consider is that RV infections that are accompanied by detection of bacterial pathogens such as S. pneumoniae are more likely to be symptomatic compared with RV infections without bacterial detection (5). Because symptomatic infections are more readily transmitted than asymptomatic infections (9, 10), cotransmission of RV and S. pneumonia (or perhaps other bacterial pathogens) could increase the probability of secondary symptomatic illnesses, and in turn could promote more efficient transmission of RV infection to other contacts.

In addition increasing the probability of symptomatic respiratory illnesses, acquisition of both RV infection and pneumococcus could increase the risk for bacterial complications of viral respiratory infections, such as otitis media, sinusitis, and pneumonia. As a consequence, treatments that prevent or lessen the severity of RV infections could secondarily reduce the spread of pneumococcal colonization and these secondary infectious complications. As new therapies or vaccines targeting RV infections progress from preclinical investigations into clinical trials, it will be of great interest to determine whether inhibition of these picornavectors for pneumococcal transmission have benefits to respiratory health that extend beyond inhibition of RV infection.